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Amiodarone is a potent antiarrythmic agent used in the treatment of refractory tachyarrythmias and premature ventricular contractions. Amiodarone may be responsible for the frequent and various side effects including corneal deposits, abnormal liver function test, hyperthyriodism or hypothyroidism, bluish discoloration of the skin, neuropathies, and the others. However, pulmonary toxicity is most serious adverse reaction limiting the clinical efficacy. Rescently, we experienced a case of pulmonary toxicity induced by low dose 10-month amiodarone treatment for atrial fibrilation with rapid ventricular response. Lung biopsy reveals interstitial inflammation, fibrosis, hyperplasia of pneumocytes, and foamy macrophages. Respiratory symptoms and abnormal chest X-ray findings were nearly complete cleared after using steroid and withdrawal of amiodarone. We report a case of amiodarone-induced pulmonary toxicity with literature review.

The possibility that circulating immune complexes (IC) could modify lipoprotein lipase (LPL) activity or release was explored in in vitro systems. IC were precipitated at antibody-Ag equivalence by using specific rabbit antisera and Ag from inactivated rubella virus and hemagglutinins from purified whole virions from three prototype strains of influenza (A/Brazil, A/Bangkok, and B/Singapore) as well as from a combined diphtheria and tetanus toxoid adsorbed with inactivated pertussis. After resolubilization, these IC were exposed to delipidated homogenates of rat epididymal fat pads before assay for LPL activity. LPL activity was stimulated two- to three-fold by the presence of 20 to 40 micrograms IC protein. This effect is not caused by the individual components of the IC because neither the specific Ag nor the individual antisera had any significant effect on LPL activity. With the rubella IC, a greater stimulatory effect was seen with increase in IC protein. With the influenza and diphtheria, pertussis, tetanus (DPT) IC, however, inhibition occurred when IC protein exceeded the amount of protein used for the LPL assay. C did not appear to be involved because IC prepared with heated antisera had similar effects. When intact rat epididymal fat pads were exposed to the rubella, influenza, or DPT IC, LPL activity recovered in the suspension medium was increased in each instance compared with pads exposed to a comparable amount of albumin. These findings may have implications for specific lipid changes that may occur during the immediate post-infectious period following rubella, influenza, or infections with the several bacteria whose Ag were present in the DPT IC used in these studies.

Co(II) carboxypeptidase A has been oxidized to Co(III) carboxypeptidase A with hydrogen peroxide. The resultant metalloprotein has an absorption spectrum different from that of the Co(II) enzyme and the metal is no longer removable by dialysis. The Co(III) carboxypeptidase A retains esterase activity comparable to that of the Co(II) enzyme and has very low peptidase activity. This demonstrates that scission of a bond to the first coordination sphere of the metal is not necessary for the hydrolysis of ester substrates.

Patients with Reye's syndrome who have been given aspirin are said to maintain higher-than-anticipated salicylate concentrations in blood, for longer than expected. We explored whether this could be attributed to spurious results from nonsalicylate compounds in the Trinder reaction for salicylates. All of 63 organic acids and amines examined that form colored complexes with Trinder's reagent had detectable absorbance at 540 nm at 0.2 g/L, including some endogenous compounds known to be increased in Reye's syndrome patients and many others endogenous in humans. By subjecting deproteinized sera to thin-layer chromatography and eluting the salicylate fraction before complexing it with ferric ion, true salicylate can be measured quantitatively and differentiated from interfering compounds. In addition, when we examined the effect of salicylate on palmitate binding to serum proteins, we found that salicylate concentrations of 0.2 g/L displaced [16-14C]palmitate binding to protein more in Reye's syndrome patients than in Reye's syndrome survivors or children with influenza. This suggests the presence of atypical binding characteristics for salicylate and palmitate in the acute disorder but not in survivors or children with influenza.

Serum and urinary urate concentrations were studied in 44 patients with homozygous sickle cell (SS) disease, and in 27 controls with normal haemoglobin. Hyperuricaemia (>0·39 mmol/l (6·5 mg/100 ml)) occurred in 41% of SS patients and inversely correlated with renal urate clearance but not with indices of bone marrow turnover. Higher serum urate concentrations occurred in patients with proteinuria, probably due to associated tubular damage. Higher serum urate concentrations and lower urate clearance occurred in males compared to females.

Cryoprecipitates were prepared by various techniques including slow-thaw, rapid-thaw, thaw-centrifuge and thaw-siphon methods. Recoveries of 42.3 +/- 9.5% for slow-thaw, 48.8 +/- 8.8% for rapid-thaw, 41.3 +/- 15.8% for thaw-centrifuge and 67.4 +/- 8.9% for thaw-siphon in factor VIII activity were obtained. These results indicated that cryoprecipitate prepared by the thaw-siphon method had the best recovery of the factor VIII procoagulant activity. However, the final volume of the plasma was rather difficult to control and there was a risk that some factor-VIII-containing materials were siphoned with the cryo-poor plasma, especially approaching the end of the process. A modified thaw-siphon method was developed which involved stopping the siphon after 60 min, centrifuging and expressing the remaining plasma to a final volume of less than 15 ml. A yield of 67.1 +/- 9.8% factor VIII activity was obtained. This product is similar to that produced by the original thaw-siphon method in yield but about half in volume.

Patients with Reye's syndrome who have been given aspirin are said to maintain higher-than-anticipated salicylate concentrations in blood, for longer than expected. We explored whether this could be attributed to spurious results from nonsalicylate compounds in the Trinder reaction for salicylates. All of 63 organic acids and amines examined that form colored complexes with Trinder's reagent had detectable absorbance at 540 nm at 0.2 g/L, including some endogenous compounds known to be increased in Reye's syndrome patients and many others endogenous in humans. By subjecting deproteinized sera to thin-layer chromatography and eluting the salicylate fraction before complexing it with ferric ion, true salicylate can be measured quantitatively and differentiated from interfering compounds. In addition, when we examined the effect of salicylate on palmitate binding to serum proteins, we found that salicylate concentrations of 0.2 g/L displaced [16-14C]palmitate binding to protein more in Reye's syndrome patients than in Reye's syndrome survivors or children with influenza. This suggests the presence of atypical binding characteristics for salicylate and palmitate in the acute disorder but not in survivors or children with influenza.

New methods for the determination of human factor VIII clotting protein (F. VIII:C) have been developed utilizing hemagglutination technique without using any other coagulation proteins in the assay. A 50% ammonium sulphate precipitate of the plasma from a hemophilic patient containing high titer of F. VIII:C inhibitor was purified on an affinity column of sepharose 4B covalently linked to F.VIII:C by CNBr. The 2.8 M MgCl2 eluted protein, after dialysis against 0.1 M phosphate buffered saline (pH 7.4), was coupled on either fresh or stabilized human erythrocytes by using either chromic acid or glutaraldehyde as the coupling agent. Serial dilutions of human plasma or F. VIII concentrate were added to the anti-F.VIII:C coated red cell suspension on a microtiter plate. For the stabilized cells, the plate was incubated on a vibration-free surface at room temperature. The results were read after two hours. For the fresh cells, the plate was incubated at room temperature for 30 minutes and was centrifuged at 300 Xg for ½ minute. It was then placed on a tilted platform at a 600 angle. The results were read after 10 minutes. By these methods, it is possible to determine the detectable level of F.VIII:C in plasma and the F.VIII:C concentration in cryoprecipitates and F.VIII concentrates.

Collagenase-treated isolated cells, prepared from epididymal fat pads of Sprague-Dawley rats exposed to 32Pi or (gamma-32P)-ATP, result in differences in label incorporation into peptides as determined by autoradiography of dried SDS polyacrylamide gels. 32Pi-labelled cells respond to epinephrine by increase in labeling of a 67,000-dalton band, presumably the activated lipase. (gamma-32P)-ATP exposed cells gave a dose-dependent increase in a 53,000-dalton band, a finding shared by cells exposed to cAMP in the absence of epinephrine. However, whereas, cAMP also significantly increased the labeling of an 18,000-dalton band, epinephrine had only a minor effect in the labeling of the 18,000-dalton component. Also, the degree of labeling of a 42,000-dalton band is diminished after epinephrine compared to unstimulated cells. By contrast, cAMP does not affect the labeling of the 42,000-dalton component. The localization of the 53,000- and the 18,000-dalton peptides as well as the enzyme(s) that catalyze their phosphorylation on the external surface of the fat cell is supported by studies using a number of macromolecular probes as well as by subcellular fractionation studies. The absence of such phosphopeptides or kinase activity in the infranatants of such cell suspensions eliminates the possibility that these phenomena are the result of leakage of cytoplasmic components. Thus, epinephrine appears to have effect and do not appear to be explicable simply by the release of cAMP to the extracellular compartment.

RBC insulin binding was examined in Reye's survivors and families of affected patients to determine whether their previously reported hyperinsulinemic responses to oral glucose are accompanied by alterations in insulin binding and could contribute to the hypercatabolism seen in this disorder. The mean (125I)-insulin binding to 3 X 10(9) RBC's was 5.7 +/- SEM 0.4 percent in survivors compared to 6.6 +/- 0.3 in siblings (p less than .05) and 6.6 +/- 0.4 in control children (p = .05). Sex and maturity differences were found with higher binding values in men than women as well as higher values in men than boys. Receptor numbers in survivors were comparable to control values. Average affinities varied widely. Plasma insulin levels were low in the fathers (9 +/- SEM 1.4 uU/ml compared to 18.3 +/- 1.8 for control men and 20 +/- 4.5 for mothers of affected patients). The acute syndrome is accompanied by hypercatabolism in the presence of increased plasma insulin levels and familial clustering of cases and recurrences are known to occur. Reduction in insulin binding may play a role in the acute disease if such is shared by more traditionally hormone-responsive cells.