The mechanism of bioactivation and antigen formation of amodiaquine in the rat.

A glutathione conjugate of amodiaquine has been isolated and characterized from rat bile after administration of [14C]amodiaquine (50 mumol/kg, 5.0 muCi/rat) to anaesthetized male Wistar rats. Thioether conjugates of amodiaquine in rat bile accounted for a total of 12% of the dose, 5 hr after administration of the drug. In addition, 1% of the dose remained in the liver covalently bound to tissue proteins after 5 hr. These findings provide direct evidence that a chemically reactive metabolite, amodiaquine quinoneimine, has been formed from the drug in vivo. A second major metabolite, desethylamodiaquine, accounting for 14% of the given dose, was present in the liver after 5 hr. Enzyme inhibition studies with ketoconazole-pretreated rats showed that both amodiaquine quinoneimine and desethylamodiaquine formation can be catalysed by cytochrome P450. The demonstration that amodiaquine readily and extensively forms a metabolite in vivo, with strong reactivity towards protein and non-protein thiol groups, may help to explain the idiosyncratic toxicity observed in man.     

A community-based epidemiologic study of health sequelae of exposure to hydrofluoric acid.

An accident at an oil refinery in Texas City, Texas, released around 40,000 lb of hydrogen fluoride, exposing the community to the highly toxic and corrosive substance. A population-based epidemiologic study was conducted to evaluate the impact of the accident on the health of the community. Exposure assessment was done using a multipronged approach through a door-to-door survey of 10,811 individuals. A symptom survey resulting in 1994 completed interviews was conducted with a stratified random sample selected from the exposure study database. The sampling was balanced with respect to age, gender, and predisposition across the three ordinal exposure categories. The results show a strong dose relationship (P < 10(-4)) between the exposure and symptoms reported following the accident and 2 years later, most notably breathing and eye symptoms. However, substantial improvement in health was reported over the 2-year period regardless of the level of exposure. Problems of recall bias and behavioral sensitization are considered and it is recognized that the study may have overestimated the effect. It is also recognized that the study may not have completely unraveled the relative importance of exposure and host response in health outcome, since the two were probably conflated in the exposure measure. Nevertheless, the independence of predisposition and reported level of exposure, the magnitude of effect and its consistency, the unmistakable dose response, the large sample size, and the mutual corroboration of various findings make it difficult to dismiss the interpretation that the hydrofluoric acid exposure indeed caused health problems in the community that continued for at least 2 years after the accident.     

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

Hepatic artery thrombosis resulting in gas gangrene of the transplanted liver.

Early hepatic artery thrombosis after orthotopic liver transplantation results in massive injury to hepatocytes and the bile duct epithelium. In the fulminate form, impaired liver synthetic function is expressed by encephalopathy and coagulopathy. Ischemic bile duct injury is associated with the disruption of the biliary anastomosis, bile duct strictures, and intrahepatic bilomas. The inability of the liver macrophages to clear translocated portal blood intestinal pathogens results in persistent bacteremia and sepsis. The major radiologic finding is the radiographic evidence of gas gangrene of the liver graft. Early recognition and correct interpretation of the radiologic findings, immediate removal of the liver graft, and placement of the patient on venous-venous bypass or total hepatic devascularization while a new liver is being procured and retransplantation are the only hope for survival.     

Employed mothers: stress and balance-focused coping.

This critical feminist grounded theory study examined how employed mothers coped with the stress of managing multiple responsibilities in family, health, and paid work. Over a 2-year period, 20 mothers employed as support staff in a large, publicly funded institution participated in repeated individual in-person and telephone interviews and in a focus group. Interviews were transcribed and analyzed using constant comparative methods. The women experienced stress from continuous demands in paid and family health work compounded by time constraints, inflexible expectations, conflicting demands, compromised personal resources, and inadequate support. Most of their coping strategies were individual, such as focusing on priorities, but some women used shared family decision-making. Findings support both individual and family stress and coping theory, yet underscore the need to explicate social-ecological influences such as relational power. Strategies that can enhance coping and reduce stress are described for nurses who work with women and families.     

Managing swabs in the operating theatre: a new method.

The swab count has traditionally used a swab rack. A new alternative 'bag' method involves placing used swabs in batches of five into plastic bags which are sealed and stored in a bin. A randomized prospective study was carried out to compare these two methods. Twenty consecutive ear, nose and throat cases were randomized to rack or bag collection. Swab-related activities were divided into three categories and analysed by formal time-and-motion criteria. Blood contamination of operating theatre and circulating personnel was recorded. The time involved in all three swab-related activities was significantly less using the bag technique. There was no theatre blood contamination using this method, but significant contamination occurred using the rack. Circulating theatre personnel were minimally contaminated in two cases using the bag method but were grossly contaminated in all ten cases using the rack method. The bag technique is therefore safe and time efficient.