Fucoidin, an inhibitor of leukocyte adhesion, exacerbates acute ischemic renal failure and stimulates nitric oxide synthesis.

OBJECTIVES: To lessen renal ischemic injury caused by fucoidin, a substance capable of reducing tissue infiltration by neutrophils, and to seek a possible interrelationship with the nitric oxide system which may also modulate leukocyte infiltration. MATERIAL AND METHODS: Acute ischemic renal failure was induced in rats by uninephrectomy followed by 60 min of clamping of the renal artery. The rats were injected with fucoidin (25 mg/kg) or fucoidin+nitroprusside (2.5 mg/kg) before reperfusion, and urine was collected for 24 h afterwards. Serum and urine were examined for creatinine sodium and protein; creatinine clearance and fractional excretion of sodium (FENa) were calculated. The renal tissue of the sacrificed animals was examined histologically for tissue damage and histochemically for myeloperoxidase, a marker of neutrophil infiltration. The nitric oxide system was evaluated by measuring urinary nitrates and inducible nitric oxide synthase messenger RNA (iNOs mRNA). RESULTS: Renal failure was more severe in the fucoidin group than the nitroprusside group (creatinine clearance 0.11+/-0.08 ml/min for ischemia+fucoidin versus 0.26+/-0.11 ml/min for ischemia only; p<0.002). Adding nitroprusside to fucoidin lessened the decline in creatinine clearance (0.13+/-0.13 ml/min; p=NS). Fucoidin was associated with greater tubular damage, as evidenced by increased FENa (7.2%+/-2.8% vs 1.51%+/-1.96% for ischemia only; p<0.001). Nitroprusside weakened this trend. Fucoidin caused an increase in the fractional excretion of nitrates, a response accompanied by increased iNOS mRNA. CONCLUSIONS: Fucoidin failed to protect the kidney from ischemic damage and was even nephrotoxic. It also stimulated the formation of iNOS RNA.

Multidrug-resistant Pseudomonas aeruginosa: risk factors and clinical impact.

Pseudomonas aeruginosa, a leading nosocomial pathogen, may become multidrug resistant (MDR). Its rate of occurrence, the individual risk factors among affected patients, and the clinical impact of infection are undetermined. We conducted an epidemiologic evaluation and molecular typing using pulsed-field gel electrophoresis (PFGE) of 36 isolates for 82 patients with MDR P. aeruginosa and 82 controls matched by ward, length of hospital stay, and calendar time. A matched case-control study identified individual risk factors for having MDR P. aeruginosa, and a retrospective matched-cohort study examined clinical outcomes of such infections. The 36 isolates belonged to 12 PFGE clones. Two clones dominated, with one originating in an intensive care unit (ICU). Cases and controls had similar demographic characteristics and numbers of comorbid conditions. A multivariate model identified ICU stay, being bedridden, having high invasive devices scores, and being treated with broad-spectrum cephalosporins and with aminoglycosides as significant risk factors for isolating MDR P. aeruginosa. Having a malignant disease was a protective factor (odds ratio [OR] = 0.2; P = 0.03). MDR P. aeruginosa was associated with severe outcomes compared to controls, including increased mortality (OR = 4.4; P = 0.04), hospital stay (hazard ratio, 2; P = 0.001), and requirement for procedures (OR = 5.4; P = 0.001). The survivors functioned more poorly at discharge than the controls, and more of the survivors were discharged to rehabilitation centers or chronic care facilities. The epidemiology of MDR P. aeruginosa is complex. Critically ill patients that require intensive care and are treated with multiple antibiotic agents are at high risk. MDR P. aeruginosa infections are associated with severe adverse clinical outcomes.

Warfarin therapy is feasible in CYP2C9*3 homozygous patients.

Background: Patients carrying variant CYP2C9 alleles are prone to bleeding complications under standard warfarin treatment. Our aim was to test the feasibility of warfarin therapy in patients with severe, inherited CYP2C9 deficiency. Methods: CYP2C9 genotypes and clinical characteristics were compared retrospectively in patients who maintain stable anticoagulation on low or regular doses of warfarin. Results: In the low-dose (10.5+/-2.9 mg/week) group (N=16), we identified six (37.6%) patients with severe CYP2C9 deficiency and three each with *2/*3 and *3/*3 genotypes as compared to none in the standard dose (39.2+/-17.9 mg/week) group (N=17). Warfarin dose (mg/week) was correlated with genotype in all patients as follows: *1/*1 (N=14) dose=33.6+/-19.4; *1/*2 (N=9) dose=30.4+/-21.6; *1/*3 (N=4) dose=15.3+/-10.7; *2/*3 (N=3) dose=10.6+/-3.6; *3/*3 (N=3) dose=7.3+/-3.1. Age and frequency of concurrent warfarin potentiating medication administration were higher in the low-dose group than in the standard dose group of patients. Conclusions: Warfarin treatment is feasible in individuals with severe, inherited CYP2C9 deficiency. Dose requirement was correlated with CYP2C9 genotype and possibly affected by age and concurrent intake of interfering drugs. Prospective studies are needed to test the feasibility and cost effectiveness of using algorithms based on these parameters for adjusting initial warfarin dose to meet individual needs.

Acute myeloid leukemia presenting as obstructive jaundice.

A 36-year-old man presented with abdominal pain and jaundice. Ultrasound examination of the abdomen showed dilatation of the intrahepatic bile ducts and a normal common bile duct. No calculi were demonstrated. A computerized tomography scan did not show any masses. A peripheral blood smear was diagnostic of acute myeloid leukemia. After remission-inducing chemotherapy, there was a complete regression of the jaundice, which had not recurred at the 12-month follow-up.

A lipid emulsion reduces mortality from clomipramine overdose in rats.

Tricyclic antidepressants are a common cause of self poisoning. Since these drugs are highly lipid soluble, we examined the interaction between imipramine and a lipid emulsion. Rats were given an iv dose of imipramine with either normal saline or a lipid emulsion as vehicle. The rats who received the lipid emulsion had a significantly lower mortality. The role of lipid emulsions poisoning therapy is reviewed.