Acquired epidermolysis bullosa treated with a gold compound.

A 20-year-old man with acquired epidermolysis bullosa of 3 years' duration was treated intramuscularly with gold sodium thiomalate. After a total dose of 1 000 mg gold sodium thiomalate, administered over a period of 9 months, the patient has shown an almost complete remission, without any apparent side effects of the chrysotherapy.     

Serum albumin and lipoproteins as the quinidine binding molecules in normal human sera.

To substantiate the binding of quinidine in human sera and predict variations of binding dissociation constants and number of binding sites were determined for separate serum proteins. Human sera were fractionated by gel filtration and ultracentrifugation, and binding was evaluated by equilibrium dialysis at pH 7·30 at 20° and 37° in a Krebs-Ringer phosphate buffer. Quinidine was bound to all serum lipoproteins and to serum albumin. The binding was influenced by the buffer composition. In sodium phosphate buffer there were two separate binding sites for quinidine on LDL and HDL, while there was only one detectable binding site on VLDL and HDL in a Krebs-Ringer phosphate buffer. On LDL also there appeared to be one binding site but it exhibited a positive cooperative binding effect at lower concentrations of quinidine. This effect was assumed to be caused by inorganic ions of the Krebs-Ringer phosphate buffer. At a therapeutic level of quinidine in normal human serum the concentration of quinidine bound to serum proteins was 1·062 × 10^?5 M. Calculated from the evaluated binding parameters VLDL contributed with 0·101 × 10^?5 M of this binding, LDL with 0·143 × 10^?5 M, HDL with 0·083 × 10^?5 M and albumin with 0·699 × 10^?5 M.     

The influence of salts and differences in protein isolation procedure on the binding of quinidine to human serum albumin

The influence of buffer and two different albumin preparations on the albumin-quinidine interaction was investigated. Human serum albumin was prepared by either alcohol fractionation or ultracentrifugation with subsequent gel filtration. The interaction between albumin and quinidine was determined by equilibrium dialysis. It was inhibited by halide ions and consequently different binding parameters were found to be valid for the complex in sodium phosphate and in Krebs-Ringer phosphate buffer. The influence of Ca²⁺, Mg²⁺ and SO^2?₄ in physiological amounts was negligible. The albumin obtained by alcohol fractionation possessed one binding site for quinidine, while the albumin isolated by ultracentrifugation with subsequent gel filtration possessed two binding sites when tested in a Krebs-Ringer phosphate buffer. In sodium phosphate buffer both albumin preparations had two independent binding sites, and showed essentially identical binding parameters.     

Differences in the serum protein binding of prazosin in man and rat

The serum protein binding of prazosin in man and rat has been studied in vitro by equilibrium dialysis. Prazosin was more extensively bound in human serum than in rat serum with binding ratios (B/F) of 14.3 +/- 3.4 and 4.4 +/- 0.2 (corresponding to 93.4 and 81.4% bound), respectively. This difference in binding between the species was partly due to qualitative differences between human and rat serum albumin, but also to the lower concentration of albumin in rat serum. Rat serum albumin (RSA) apparently showed two different classes of binding sites for prazosin, one with high (KD = 5.78 X 10(-6) M) and one with low (KD = 1.1 X 10(-4) M) affinity; the former is suggested as representing alpha 1-acid glycoprotein (alpha 1-AGP) with one binding site for prazosin per molecule, the latter as representing RSA with 0.28 binding sites per molecule. Human serum albumin (HSA) and human alpha 1-AGP both showed one class of binding sites with KD values of 2.7 X 10(-5) and 1.95 X 10(-6) M, respectively. HSA possessed 0.5 and human alpha 1-AGP 1 binding site for prazosin per molecule. The binding parameters obtained for the isolated serum proteins overestimated to some degree the total serum protein binding of prazosin in man. This was explained by a specific deviation from the law of mass action. HSA was the major binding protein in human serum at therapeutic concentrations, with ca. 60% of the total binding, the remaining 40% being bound to alpha 1-AGP. Anticipating that the high affinity binding site on the RSA preparation represents the binding of prazosin to alpha 1-AGP, then this protein accounts for 70% of the binding in rat serum, while rat serum albumin accounts for approximately 23%. The binding of prazosin to lipoproteins was insignificant in both species. The observed differences between man and rat in the serum protein binding of prazosin implicate differences in the two species with respect to prazosin pharmacokinetics and the pharmacological effect.     

Open reduction and internal fixation of displaced intraarticular fractures of the distal radius: 31 patients followed for 3-7 years

We have used open reduction and internal fixation with a T-plate in 31 displaced, intraarticular fractures of the distal radius which were judged irreducaible or in which closed reduction failed. The mean follow-up time was 4 (3-7) years. The dorsal angulation, the radial length, the articular step-off and the intraarticular gap between fragments were substantially improved after surgery. 30 patients had excellent or good extraarticular alignment, and only 1 patient had a postoperative intraarticular step-off of 2 mm. The function was excellent or good in 26 patients at follow-up. Complications occurred in 6 patients: 1 compartment syndrome, 1 postoperative wound infection, 2 ruptures of the extensor pollicis longus tendon, and 2 patients had median nerve paresthesias.     

Complications that may occur in those with spinal cord injuries who participate in sport

The purpose of this study was to determine the risk of developing complications in paraplegics taking part in sport. It is a retrospective study of patients with complete spinal cord injury at the spinal level of C7--cauda equina/conus injury, and consists of 61 patients admitted to the Beitost?len Healthsportcenter, Norway. All of them had achieved satisfactory bladder/bowel function. The wheelchair dependents were all skilled in the use of the wheelchair. They participated in a training programme with an average duration of 25 days. Different activities were tried, such as weight-lifting, pulking, swimming, volleyball, calisthenics in a group, horseback-riding, archery, tabletennis, canoeing, totalling 11 955 training hours. During the training period the following complications were observed: urinary tract infections, pressure sores, and sprains and strains. There were 30 complications, most of them only of minor type. The incidence of complications, expressed as number of complications/1000 training-hours was, for urinary tract infections--0,50, pressure sores 0,42, sprains/strains 1,33, others 0,25: in all 2,51. Sprains and strains were the most common complications, accounting for about 55 per cent of the total, all of which were successfully treated before discharge. Sport activities are an important part of the rehabilitation of the spinal cord injured and the risk of serious complications appears to be low.     

Species differences in short term toxicity from inhalation exposure to bromobenzene

Lung, liver and kidney injury were studied in mice, rats and rabbits 48 h after termination of a 4 h inhalation exposure to bromobenzene vapour (250–3400 ppm). Light and electron microscopy of lung tissue revealed injury to Clara cells and adjacent epithelium in mouse bronchioli (bromobenzene concentration 250 ppm and 1000 ppm) and to Clara cells of rat bronchi and bronchioli (1000 ppm bromobenzene) and of rabbit bronchi (2500 ppm and 3400 ppm). Histological and clinicochemical indices of liver damage were found in the same animals, whereas kidney toxicity was observed in mice (two out of ten showed tubular necrosis and elevated concentration of plasma urea) and rats (all had elevated plasma concentrations of creatinine) exposed to 1000 ppm bromobenzene. Inhalation exposure thus produced less kidney injury than expected from previous studies with equimolar doses given intraperitoneally. The mouse was the most severely affected species, followed by the rat, and lastly the rabbit. The animal susceptibility could not be ranked according to the rate of¹⁴C-bromobenzene covalent binding in lung or liver, but it was inversely related to the rate of N-demethylation of benzphetamine (indicative of P450IIB activity) in both lung and liver microsomal preparations. Differences in a P450 mediated detoxification could therefore be of importance in species variability to bromobenzene injury.