Membranous glomerulonephritis in renal allografts.
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Biomedical subjects
Publications and source records attributed to W E Smith.
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Total serum copper and ceruloplasmin oxidase activities have been measured over a 24-h period in rats and guinea-pigs treated with 100 mg/kg body weight of copper (II) aspirinate. In the rat, administration s.c. produced higher total serum copper levels than oral administration at all time intervals studied, whereas in the guinea-pig, oral administration produced the higher level after 1 h and s.c. administration the higher level after 5 h. In both species, the rate of elimination of the additional copper was faster following oral administration. Ceruloplasmin oxidase activity appeared to be inhibited in certain cases but rose in all cases except for orally treated rats after 24 h. The initial rise in serum copper was due mainly to copper present on albumin. The increased albumin copper was detected directly by electrophoresis of serum samples and subsequent determination of the copper level in the portions of the strip which contained proteins. After s.c. administration to the rat, the amount of ultrafilterable copper was raised by a detectable amount. 7 h after s.c. or oral administration of copper aspirinate, the thiol concentration of the serum was reduced in both rats and guinea-pigs. The relationship of these levels to the anti-inflammatory action of copper (II) aspirinate in rats and guinea-pigs is discussed.
Several gold salts were compared in kaolin-induced rat paw oedema, u.v. erythema in guinea pigs, delayed type hypersensitivity and humoral immunity in mice, and adjuvant-induced arthritis in the rat. In the latter the additional parameters of serum gold and copper levels and lysosomal enzyme activity were determined. In addition, the in vitro inhibition of several lysosomal enzymes derived from mouse macrophages was studied. The gold compounds examined were aurothiomalate, aurothioglucose, triethylphosphine gold chloride (SK & F 36914) and its glucopyranoside derivative (SK & F D-39162), triphenylphosphine gold chloride and sodium gold chloride dihydrate. SK & F 36914 and SK & F D-39162 has significant activity after oral dosage upon paw kaolin and u.v. erythema in rats and guinea pigs, respectively. Gastric swelling also occurred. In Wistar rats, adjuvant arthritis was little affected by the gold salts but in the Lewis rats there was suppression. In both strains there was less elevation in serum copper levels with treatment by SK & F 36914 and SK & F D-39162, but not by aurothiomalate. None of the compounds had any measurable effect on delayed hypersensitivity or humoral antibody levels in mice. The in vitro activities of cathepsin B1 and cathepsin D were inhibited by all the gold compounds. Reactivity of gold compounds with glutathione and cysteine in vitro was dependent on compound solubility and the nature of the gold ligand. Considerable differences exist between the profiles of activity for the different gold salts evaluated. These observations indicate that some gold salts do possess anti-inflammatory activity with a potency similar to that of indomethacin.
Copper complexes of a range of ligands have been prepared and evaluated for antiinflammatory activity and irritancy after oral, subcutaneous, and local administration in rats and guinea pigs. The antiinflammatory activities were found to depend on the species used and the route of administration. When nonantiinflammatory ligands were used, the response was generally dose dependent. With D-penicillamine and when the ligands were themselves antiinflammatory in animal models of inflammation--as was the case with flufenamic acid, levamisole, aspirin, L-histidine, and 2-amino-2-thiazoline--differences in antiinflammatory activity were observed between the copper complexes and the free ligands. In some cases, the copper complexes were the more effective. There was a weak correlation between local (subplantar) irritation and the dose of copper but, for four compounds studied in more detail, the response in the local subplantar test and degree of antiinflammatory activity were not related, suggesting that the action of copper is not solely by a counterirritant mechanism. No obvious differences between the activities of copper(I) and copper(II) compounds were observed, suggesting that a common metabolite may be involved in the antiinflammatory action of copper.
This article identifies the scope of activities, needs and subjects of a clinical pharmacy service program in a progressive community hospital. Even after ten years of constant effort, a comprehensive hospital clinical pharmacy program still requires continual review, changes, and improvements.
Intrathoracic tumours were induced in Syrian golden hamsters given intrapleural injections of chrysotile, tremolite or glass fibres; but the carcinogenicity of these materials was reduced or disappeared with reductions in fibre size. After lifetime administration of UICC amosite in drinking-water, a peritoneal mesothelioma, a pulmonary carcinoma and two early squamous-cell carcinomas of the forestomach were found in 4 of 180 hamsters. No tumours related to treatment were found in animals exposed to fibre-shaped particles of cummingtonite/grunerite, mineralogically related to amosite but of shorter length.
The results of an evaluation of the use of atomic absorption spectrometry with carbon furnace atomisation to analyse the copper content of individual protein fractions separated by electrophoresis is reported. Albumin copper levels in patients with rheumatoid arthritis were found to be about 1 to 2% of the total serum copper. Both albumin and alpha 2 levels are affected by contamination from residual copper present on the strip. An investigation of this contamination indicated very low blank copper levels in the areas of the strip containing alpha 1 and beta proteins. These results, and the results of analysis of copper in the ultrafiltrate from the same serum samples, are combined to define the copper distribution in a group of patients with rheumatoid arthritis. The determinations that can most readily be carried out by this technique are discussed.
Total serum copper levels produced by the administration of a single dose of cuprous oxide (500 mg/kg) both s.c. and orally to rats and guinea pigs are reported 1, 5, 7 and 24 h after administration, together with caeruloplasmin oxidase activities and changes in the sulphydryl group concentrations. The highest serum copper levels were obtained one hour after oral administration to the guinea pig. Both animal species exhibited increased serum copper levels after s.c. administration and this increase persisted for a longer time than after oral administration. Caeruloplasmin oxidase activity varied in a complex manner and sulphydryl group activity was significantly depressed in all cases except after s.c. administration to the guinea pig. The latter results must be treated cautiously since they may indicate interactions between copper and the test procedures. Analysis of serum fractions separated by electrophoresis indicated that the absorbed copper is mainly transported on albumin. The dissolution of cuprous oxide by amino acids and hydrochloric acid and the absorption of cuprous oxidcations of the results are discussed in terms of their relevance to pharmacological and clinical studies.
Total serum copper and ultrafilterable copper levels in patients with rheumatoid arthritis were determined and related to articular index, erythrocyte sedimentation rate (ESR), and serum iron concentration. Relationships were found between serum copper and ESR, and between ultrafilterable copper and articular index. The relationship between serum copper and serum iron was found to be a drug-dependent.
A method of charging for pharmaceutical services is described which includes the cost of drug products, dispensing fees for intravenous drug admixtures, per diem fees for basic dispensing and clinical services (according to patient type), and fees for special clinical services. The basic per diem charge covers drug purchasing and inventory control, department management, drug information services, dose preparation, drug order interpretation, drug therapy monitoring, and the availability of pharmacists to answer the questions of nurses and physicians. The clinical services for which special fees are charged are: hemogram drug report, drug liver function report, aminoglycoside dosing guidelines, heparin i.v. infusion, oral anticoagulation, patient drug history, operant conditioning, parenteral nutrition guidelines, and pharmacokinetic drug level interpretations and consultations. The reasons for changing to the system, the services provided and experiences with the system are discussed. Implementation of the system is discussed in relation to the calculation of fees; comparisons with alternate charging methods; approval of special clinical service charges; computer billing; information about pharmacy charges for patients; and third-party payers.
The potential for developing a drug-use profile from drug-charge records was studied at an 830-bed community hospital. Patient drug charges were reviewed retrospectively for one year (1975) to identify: (1) which key drugs accounted for a high percentage of cost and usage; (2) where key drugs were used within the hospital; (3) how they were used; and (4) who were the chief prescribers. Of the drugs used, 8% accounted for 80% of total drug product costs. Seven drug groups (10% of the total drug groups) appeared in the top 10 of both drug cost and quantity categories. Six individual drugs also appeared in the top 10 of both categories. According to cost, cephalosporin antibiotics were ranked first among drug groups but were sixth according to quantity. Analgesics-antipyretics were ranked first among drug groups by quantity and second by cost. Cephalothin was ranked first among individual drugs by cost and was not in the top 10 in quantity. Diazepam was ranked first among individual drugs by quantity and third by cost. Patients' drug-charge records can be used effectively to generate drug-use profiles for ongoing drug use review, quality assurance and cost containment programs.
Serum levels after oral administration of 30 mg/kg of sodium aurothiomalate (Myocrisin), triethylphosphine gold chloride, or triphenylphosphine gold chloride to guinea pigs indicated that all were orally absorbed. However, the serum gold level of triethylphosphine gold chloride was three to four times that of Myocrisin or triphenylphosphine gold chloride and was comparable with the serum level produced when the same dose of Myocrisin was injected intramuscularly. A comparative time-course study between intramuscular administration of Myocrisin and oral administration of triethylphosphine gold chl;ride indicated that during the first 24 hours after intramuscular injection of Myocrisin, a large fraction of the gold was not protein-bound, whereas all detectable gold in serum after oral administration of triethylphosphine gold chloride was protein-bound. Gold levels in the separated protein fractions indicate that the gamma-globulin level after oral administration of triethylphosphine gold chloride is approximately three times higher after 24 hours than with intramuscular Myocrisin.
A comparative study of tissue gold levels produced in guinea-pigs after the oral administration of either triethylphosphine gold chloride or Myocrisin (sodium aurothiomalate) or after the injection of Myocrisin intramuscularly is reported. Gold concentrations were determined 5, 24 and 168 hours after administration in stomach, small intestine, large intestine, kidney, liver and spleen and 5 and 24 hours after administration in skin, adrenals, heart, lung and brain. In gastrointestinal tissues, tissue gold concentrations were highest with triethylphosphine gold chloride. The stomach gold level 5 hours after oral administration of triethylphosphine gold chloride is particularly high and, taken in conjunction with the other gastrointestinal gold levels measured, suggests that a stomach rather than an intestinal absorption mechanism may predominate. A more extensive time-course study on kidney and liver is reported and the possible relationship between tissue concentration and toxicity is discussed.
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