Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.     

Insulin reduces the BOLD response but is without effect on the VEP during presentation of a visual task in humans.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an invaluable tool in the assessment of in vivo neuronal activation. Quantification of the BOLD response is determined by the hemodynamic and metabolic changes that occur in response to brain stimulation. However, these changes may vary by changes in insulin, a hormone known to be vasoactive in some tissues. To determine if insulin has an effect on fMRI, we measured the BOLD response to a visual stimulus in five normal volunteers in which insulin was first suppressed and then brought to a high physiological concentration. In addition, we also examined the effect of insulin on activation of the visual cortex as measured by the visual-evoked potential (VEP). We found that the BOLD response measured in the presence of insulin (serum insulin=236+/-29 pmol/L) was significantly lower (P<0.001) than that measured in its absence (serum insulin=8+/-2 pmol/L). Insulin was without effect on P100 amplitude or latency acquired in the presence or absence of insulin in 28 subjects using the same stimulus as that used for the fMRI experiments. Our observations suggest that insulin may have effects on cerebral blood flow and/or metabolism that affect the BOLD signal that are independent of its effects on neuronal activation identified by event related potentials (ERP). These findings highlight the complexity that must be considered when interpreting differences in fMRI responses between groups of subjects that differ in insulin concentration and/or insulin sensitivity.     

Lead poisoning in six captive avian species

Red-winged blackbirds (Agelaius phoeniceus), brown-headed cowbirds (Molothrus ater), common grackles (Quiscalus quiscula), mallards (Anas platyrhynchos), northern bobwhites (Colinus virginianus), and eastern screech-owls (Otus asio) were poisoned with a concentration of lead (Pb) acetate in the diet which was increased by 60% each week until half of the birds in each treatment group died; surviving birds and all control birds except screech-owis were then killed by euthanasia. An additional group of mallards was poisoned with Pb shot. The gizzards of mallards poisoned either way usually were stained with bile; some of these birds also had proventricular impaction. Most poisoned birds of the other species were emaciated but lacked other gross lesions caused by Pb poisoning. In birds other than mallards, Pb poisoning could not be diagnosed without histological or hematological examinations or analysis of tissues. Poisoned birds of all six species could be reliably separated from control birds by an increase in the protoporphyrin concentrations in the blood and by a decrease in the activity of delta-aminolevulinic acid dehydratase (ALAD) in red blood cells. Hepatic iron (Fe) concentrations varied so much among individual birds that even though median hepatic Fe concentrations increased in poisoned birds, hepatic Fe concentrations were not useful in identifying poisoned birds. Renal intranuclear inclusion bodies occurred in 83% of all birds dying from Pb poisoning. Nephrosis, myocardial necrosis, and arterial fibrinoid necrosis were occasionally present. Median hepatic Pb concentrations varied from 20 ppm (wet wt) in male red-winged blackbirds to 111 ppm in female northern bobwhites. Median renal Pb concentrations varied from 22 ppm in redwinged blackbirds to 190 ppm in female northern bobwhites. Hepatic and renal Pb concentrations varied substantially among birds within each species. Median hepatic and renal Pb concentrations of birds that died were not statistically different (p > 0.05) from those of birds that were killed. Lead shot and Pb acetate affected mallards similarly.     

Effects of selective dopamine-1 receptor activation on intraocular pressure in man

The lack of specific agonists and antagonists has, until recently, precluded investigation of a role for dopamine receptors in the control of intraocular pressure. In the present study, we have examined the effects of fenoldopam, a novel selective dopamine1 (DA1) receptor agonist, on intraocular pressure, in eight healthy human volunteers. Fenoldopam, infused intravenously at 0.5 micrograms kg-1 min-1, increased intraocular pressure from 14.6 +/- 0.9 to 17.6 +/- 1.4 mmHg (P less than 0.05) while a control saline infusion had no effect. Pupil diameter and blood pressure did not change. In the same subjects, i.v. norepinephrine or angiotensin II both increased intraocular pressure--from 13.8 +/- 1.4- to 17.6 +/- 1.4 mmHg and from 13.4 +/- 1.3- to 17.5 +/- 1.7 mmHg respectively (P less than 0.05), and mean arterial pressure by about 20 mmHg. These data suggest that: (1) DA1 receptor activation can modulate intraocular pressure; (2) the intraocular pressure effects of the DA1 receptor agonist, fenoldopam, are independent of changes in systemic blood pressure, in contrast to those of norepinephrine or angiotensin II where intraocular and systemic blood pressures increase in parallel; (3) the ability of a DA1 receptor antagonist to lower intraocular pressure merits investigation.     

Thoracoscopic Assisted Pneumonectomy

A lung carcinoma with tumor involving more than one lobe or in close proximity to the mainstem bronchus often requires pneumonectomy for surgical cure. Inflammation, bulky tumors, and dense adhesions limit the operative field of vision and may result in the abandonment of procedures with potential for complete extirpation. This case illustrates the utility of thoracoscopy in visualization of the hilum and other neurovascular structures in a patient with a proximal tumor and dense intrathoracic adhesions. Successful resection was made possible by use of combined open and thoracoscopic modalities.     

Pyretic action of low doses of gamma-hydroxybutyrate in rats

gamma-Hydroxybutyrate (GHB) has been found to have a biphasic effect on body temperature with increased body temperature after low doses (5-10 mg/kg) and decreased body temperature after high doses (300-500 mg/kg). Brain levels of GHB between 30 and 60 min post-injection of GHB were not altered by the low doses (5-10 mg/kg), although a dose of 200 mg/kg produced a large increase in the brain concentration.