Lung hydrolases in paraquat poisoning: early response of alkaline phosphatase

In order to evaluate the early response of the alveolar epithelium following lung injury, male Long-Evans adult rats (280-350 g) were treated with a single dose (30 mg/kg, ip) of the herbicide paraquat. No animal died during the 72 h that followed the acute administration of the herbicide. When compared to control, total lipid, phosphatidylcholine, and disaturated phosphatidylcholine contents of lung homogenates from the paraquat-treated rats were significantly reduced 48 h postdose (respectively 10, 24, and 37%). Comparatively, the total lung alkaline phosphatase activity was significantly reduced as early as 12 h postdose, and by 48 h the activity had decreased by approximately 50%. Although a significant decrease in total lung acid phosphatase activity was observed 24 and 48 h after the treatment, the effect was much less than with the alkaline phosphatase activity (15% versus 50%, respectively). The lysosomal beta-N-acetylglucosaminidase and the cytoplasmic lactate dehydrogenase activities were not affected by the herbicide treatment. A subcellular fractionation of the treated lungs showed that 48 h postdose, the total alkaline phosphatase activities associated with lamellar body and surfactant fractions were decreased respectively by 60% and 49%. Due to the intrinsic association of a strong alkaline phosphatase activity with the pulmonary surfactant system, these data suggest that the monitoring of the alkaline phosphatase activity in lung fractions could represent an early and sensitive indicator of toxicity to the alveolar epithelium, most probably to type II cells.     

Serologic investigation of fatal hemolytic anemia associated with a multiple drug history and Rh-like autoantibody

A patient who expired during an episode of gross intravascular hemolysis had a complex medical history, including renal disease, Coombs positive anemia of unclear etiology, recent transfusion, and cholecystectomy. Drug history included 21 different medications, including penicillin, acetaminophen, procainamide, furosemide, sulindac, and tolmetin, all of which have been associated with a positive direct antiglobulin test or drug-induced hemolytic anemia. The patient had a history of recent use of three chemically similar nonsteroidal anti-inflammatory drugs: tolmetin (Tolectin), sulindac (Clinoril), and ketorolac (Toradol). Only tolmetin and furosemide (Lasix) antibodies were demonstrable in the patient's serum at the time of her final admission. The patient's serum at final admission contained panagglutinating IgG and IgM antibody with a titer of 1:80 using a pool of R1R1 and R2R2 screening cells. When tolmetin was added to the test system, the titer increased to 1:2,560. The direct antiglobulin test was 3+ (IgG and C3d,b). Eluates contained an Rh-like antibody compatible only with Rh deletion cells, and anti-tolmetin antibodies detected when the drug was added to the eluate in the presence of Rh deletion cells. Allogeneic adsorbed sera contained anti-tolmetin antibodies with a titer of 1:10 and a weakly reactive IgM antibody to furosemide. Antibodies to tolmetin and furosemide were apparent only when the drugs were added to sera or eluates, not with drug-coated cells. Because of the patient's complex medical history, it was not possible to attribute the fatal autoimmune hemolytic anemia solely to drug antibody.     

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP- sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.      

From asylum to mental health: is the patient any better off?

The author offers a few reflections on the theme of the recent symposium of the Quebec Hospital Association: "De l'espoir à la Réalité" ("From Hope to Reality"). Twenty-five years after the report on quebec's psychiatric hospitals, what has become of the hopes and concerns of that time? Through all the changes that have occurred--from the hopes inherited from 1960 to the hopes articulated in the 1980s; from the "outmoded" realities of the institutional model to the realities considered "the way of the future", based on an ecological or bio-psycho-culturo-social model; from the preoccupations of the asylum to those of "mental health"--a fundamental question remains: Is the patient any better off? One might add a second question: WHich 'patient' are we referring to?