Percutaneous management of emboli associated with hot tip laser-assisted angioplasty

We describe the percutaneous management of emboli that occurred in 3 patients during hot tip laser-assisted angioplasty procedures. One embolus was lysed with direct, local infusion of urokinase using an open-ended guidewire. Another embolus was removed using the transcatheter aspiration technique. The third embolus was partially lysed and then, using a steerable guidewire, displaced into a distal side branch. In all 3 cases of embolization, distal blood flow was reestablished using percutaneous techniques, obviating the need for surgical intervention.     

Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?

Homocysteine may have deleterious effects on the cardiovascular system. It has been hypothesized that these effects may be brought about by a decrease in the adenosine concentration via the S-adenosylhomocysteine hydrolase reaction. A requirement for this causal relationship is proof of a reduction in vascular adenosine concentration during conditions of elevated homocysteine concentrations. In the present communication we summarize published data obtained during systematic variation of the arterial homocysteine concentration. Most of the results reported show that an increase in homocysteine concentration to 100 microM is associated with a 20-50% decrease in vascular adenosine concentration and an increase in tissue S-adenosylhomocysteine level. Homocysteine effects on the adenosine concentration seem to be more pronounced under conditions of impaired oxygenation. Further experiments, in particular on organs and tissue that release high amounts of homocysteine, i.e., the liver, are warranted to study the potential effects of homocysteine on vascular and tissue adenosine concentrations and consequent effects on organ function. The evidence obtained may be relevant for future assessment of risk indicators in conjunction with homocysteine pathogenicity, which might potentially be extended to measurements of adenosine or S-adenosylhomocysteine levels.     

Transmission of breast cancer by a single multiorgan donor to 4 transplant recipients

We report 4 cases of breast cancer transmission to transplant recipients from a single organ donor that occurred years after donation. The diagnosis of breast cancer was occult at the time of donation. All of the recipients developed a histologically similar type of breast cancer within 16 months to 6 years after transplantation. Three out of 4 recipients died as a result of widely metastasized disease. One of the recipients survived after transplant nephrectomy followed by cessation of immunosuppression and chemotherapy. This extraordinary case points out the often fatal consequences of donor‐derived breast cancer and suggests that removal of the donor organ and restoration of immunity can induce complete remission.     

Preferences for current health and their association with outcomes in patients with kidney disease

BACKGROUND: Patients with chronic disease who express stronger preference for their current health might be expected to have better outcomes than patients who assign lower utility to their current health state. OBJECTIVE: We sought to examine associations between preferences for current health and outcomes in a national cohort of incident hemodialysis patients. METHODS: In 567 patients treated at 74 clinics, we measured patients' preferences by time trade-off on a 0-1 scale (1=willingness to sacrifice no life expectancy to achieve perfect health; 0=zero value of current health). Associations between these preferences and outcomes were examined with Poisson (hospitalization), logistic (progression of comorbidity and clinical performance), and Cox proportional hazards (mortality) models. RESULTS: The distribution of preference scores was skewed, with a mean of 0.69 and a median of 0.83. Highest (1.0) scores were associated with decreased incidence of hospitalization (incidence risk ratio=0.88, 95% confidence interval=0.80-0.97), relative to the lowest (<0.50) scores, a finding that was consistent across gender and race, with women and white subjects having greater decreases (Pinteraction<0.001). Higher preferences for current health also were associated with less worsening of comorbidity. Adjusted risks of death for patients with intermediate (>or=0.50-1.0) and the highest preference scores for current health were not different from those with lower scores. CONCLUSION: In patients with chronic kidney disease, a stronger preference for current health is associated with lower hospital admission rates and improved comorbidity but not better survival.     

Behavioral characterization of the novel GABAB receptor-positive modulator GS39783 (N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine): anxiolytic-like activity without side effects associated with baclofen or benzodiazepines

The role of GABAB receptors in various behavioral processes has been largely defined using the prototypical GABAB receptor agonist baclofen. However, baclofen induces sedation, hypothermia and muscle relaxation, which may interfere with its use in behavioral paradigms. Although there is much evidence for a role of the inhibitory neurotransmitter GABA in the pathophysiology of anxiety, the role of GABAB receptors in these disorders is largely unclear. We recently identified GS39783 (N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine) as a selective allosteric positive modulator at GABAB receptors. The aim of the present study was to broadly characterize the effects of GS39783 in well-validated rodent models for motor activity, cognition, and anxiety. The following tests were included: locomotor activity in rats and mice, rotarod and traction tests (including determinations of core temperature) in mice, passive avoidance in mice and rats, elevated plus maze in rats, elevated zero maze in mice and rats, stress-induced hyperthermia in mice, and pentobarbital- and ethanol-induced sleep in mice. Unlike baclofen and/or the benzodiazepine chlordiazepoxide, GS39783 had no effect in any of the tests for locomotion, cognition, temperature, or narcosis. Most interestingly, GS39783 had anxiolytic-like effects in all the tests used. Overall, the data obtained here suggest that positive modulation of GABAB receptors may serve as a novel therapeutic strategy for the development of anxiolytics, with a superior side effect profile to both baclofen and benzodiazepines.