1 Chloroquine was given in 300 mg single doses as an i.v. infusion, an oral solution and as tablets at intervals of at least 56 days to 11 healthy volunteers. Concentrations of chloroquine and its metabolite desethylchloroquine were measured in plasma, erythrocytes and urine using h.p.l.c.

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The triiodinated angiographic contrast medium, iothalamate, has (usually labelled 125I) been used extensively as a marker for glomerular filtration. We have studied the renal handling of 125I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51Cr-EDTA (EDTA) at 37 degrees C; a difference that was abolished at 0 degree C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice (P less than 0.05) that of EDTA (CEDTA) or 3H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1% (P less than 0.01; N = 10). After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced (P less than 0.01) and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% (P less than 0.01) before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% (P less than 0.05) by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% (P less than 0.005) and 22% (unchanged) for PAH and EDTA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Little information is available on the toxicity of monochloroacetic acid. We report the case of a 38 year-old man who was splashed with an 80% monochloroacetic acid solution on 25-30% of his body surface. In addition to epidermal and superficial dermal burns, features of systemic poisoning occurred within a few hours including disorientation, agitation, cardiac failure and coma. He later developed severe metabolic acidosis, rhabdomyolysis, renal insufficiency and cerebral edema, and died due to uncal herniation on d 8. The 4 h post exposure plasma monochloroacetic acid concentration was 33 mg/L confirming skin absorption. In addition to its corrosive action, monochloroacetic acid probably blocks the tricarboxylic acid cycle (Kreb's cycle) and may also react with sulfhydryl groups in enzymes, causing severe tissue damage in energy-rich organs.

A sensitive gas chromatographic-mass spectrometric method enabled us to study intrathyroidal concentrations of methimazole in 20 euthyroid patients with Graves' disease on treatment with carbimazole and T4. There was no difference between patients receiving a final dose of carbimazole (10 mg), known to be totally bioactivated to methimazole (6.1 mg), 3-6 h before thyroid excision (518 ng/g thyroid tissue +/- 90 SEM) and patients who received the same dose 17-20 h before excision (727 ng/g thyroid tissue +/- 157 SEM), indicating a slow intrathyroidal turnover of the drug. On the other hand, the serum concentrations were much higher in the first group (102 ng/ml +/- 5 SEM vs. 16 ng/ml +/- 3 SEM), reflecting a short plasma half-life of the drug. The intrathyroidal concentrations of methimazole ranged from 230-1895 ng/g among individual glands but were similar in pieces from different parts of a single gland. These methimazole concentrations are lower than the concentrations reported by others to have an immunosuppressive action on lymphocytes in vitro.

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The effects of peroperative electrical calf muscle stimulation with groups of impulses giving a short lasting tetanus of the calf muscles on postoperative deep venous thrombosis (DVT) and pulmonary embolism (PE) were compared with that of dextran 40 given per and postoperatively. The incidence of DVT and PE during the first 4-6 postoperative days was recorded. The diagnosis of DVT was based on the 125I-fibrinogen uptake test and phlebography and of PE on pre- and postoperative perfusion pulmonary scintigram and chest X-ray examination. Both methods reduced the incidence of PE. Calf muscle stimulation reduced the DVT incidence in patients with malignant disease while the reduction in DVT incidence for the whole group only was significant in the stimulation as well as the dextran 40 group. Mean values for preoperatively determined levels of antithrombin III, beta-thromboglobulin, fibrinopeptide A, plasminogen and ability to release fibrinolytic activity during venous stasis did not differ between those patients who developed or those who did not develop postoperative DVT or PE. However, antithrombin III levels below 80 per cent appeared to predispose to postoperative thromboembolism. The two prophylactic methods have similar effects on the incidence of postoperative thromboembolism. The stimulation method has certain advantages due to its safety and simplicity.