The Effect of Flurbiprofen on Steady-State Plasma Lithium Levels

Study Objective . To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium. Design . Placebo-controlled, single-blind, crossover study. Setting . University-affiliated hospital. Patients . Eleven healthy women with bipolar disorder. Interventions . The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study. Measurements and Main Results . Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (C_min) and area under the curve were statistically significantly increased (p<0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in C_min appeared to be associated with a greater than 1000-μg/24 hour decrease in urinary excretion of prostaglandin E₂. Conclusion . Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.     

Temporal relationship of hepatocellular dysfunction and ischemia in sepsis

To determine whether hepatic dysfunction in sepsis results from hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent either cecal ligation and puncture or sham operation. After either two or six hours, effective hepatic blood flow was measured using the galactose clearance method. Hepatocytes were isolated and intracellular sodium and potassium and glucose production were measured. Hepatic blood flow in septic rats decreased as early as two hours after sepsis when compared with sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight). Intracellular sodium and potassium levels and glucose production in septic rats were not significantly different when compared with controls at two hours. After six hours, hepatic blood flow remained depressed and intracellular sodium level was increased compared with sham-operated rats (41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9 mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs 111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose production was decreased in septic rats after six hours when compared with controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data suggest that hepatic blood flow is decreased before alterations in intracellular sodium and potassium as well as glucose production.     

Comparison of seizure detection algorithms in continuously monitored pediatric patients.

SUMMARY: Robust, automated seizure detection has long been an important goal in epilepsy research because of both the possibilities for portable intervention devices and the potential to provide prompter, more efficient treatment while in clinic. The authors present results on how well four seizure detection algorithms (based on principal eigenvalue [EI], total power, Kolmogorov entropy [KE], and correlation dimension) discriminated between ictal and interictal EEG and electrocorticoencephalography (ECoG) from four patients (aged 13 months to 21 years). Test data consisted of 46 to 78 hours of continuously acquired EEG/ECoG for each patient (245 hours total), and the detectors' accuracy was checked against seizures found by a board-certified neurologist and an experienced registered EEG technician. The results were patient-specific: no algorithm performed well on a 13-month-old patient, and no algorithm consistently performed best on the other three patients. One of the metrics (EI) supported the existence of a postictal period of 5 to 15 minutes in the three oldest patients, but no strong evidence of a preictal anticipation was found. Two metrics (EI and KE) cycled continuously with a period of several hours in a 21-year-old patient, highlighting the importance of continuous analysis to differentiate background cycling from anticipation.     

Contributions of ion conductances to the onset responses of octopus cells in the ventral cochlear nucleus: simulation results

The onset response pattern displayed by octopus cells has been attributed to intrinsic membrane properties, low membrane impedance, and/or synaptic inputs. Although the importance of a low membrane impedance generally is acknowledged as an essential component, views differ on the role that ion channels play in producing the onset response. In this study, we use a computer model to investigate the contributions of ion channels to the responses of octopus cells. Simulations using current ramps indicate that, during the "ramp-up" stage, the membrane depolarizes, activating a low-threshold K(+) channel, K(LT), which increases membrane conductance and dynamically increases the current required to evoke an action potential. As a result, the model is sensitive to the rate that membrane potential changes when initiating an action potential. Results obtained when experimentally recorded spike trains of auditory-nerve fibers served as model inputs (simulating acoustic stimulation) demonstrate that a model with K(LT) conductance as the dominant conductance produces realistic onset response patterns. Systematically replacing the K(LT) conductance by a h-type conductance (which corresponds to a hyperpolarization-activated inward rectifier current, I(h)) or by a leakage conductance reduces the model's sensitivity to rate of change in membrane potential, and the model's response to "acoustic stimulation" becomes more chopper-like. Increasing the h-type conductance while maintaining a large K(LT) conductance causes an increase in threshold to both current steps and acoustic stimulation but does not significantly affect the model's sensitivity to rate of change in membrane potential and the onset response pattern under acoustic stimulation. These findings support the idea that K(LT), which is activated during depolarization, is the primary membrane conductance determining the response properties of octopus cells, and its dynamic role cannot be provided by a static membrane conductance. On the other hand, I(h), which is activated during hyperpolarization, does not play a large role in the basic onset response pattern but may regulate response threshold through its contribution to the membrane conductance.     

Changes in food intake and activity after quitting smoking

Quitting smoking often results in weight gain. The causes of the gain are not known. The present study evaluated changes in calories, total sugars, sucrose, fat, protein, and nonsugar carbohydrates as well as changes in activity levels after quitting smoking. Ninety-five subjects were randomly assigned to either early (Week 2) or late (Week 6) quit dates. Subjects were assessed on weight, food intake, activity levels, and smoking levels at baseline, at Weeks 4 and 8, and at Weeks 12 and 26 postquit. The results indicated significant increases in calories, sucrose, and fats 2 weeks after the quit date. Changes for total sugars were less consistent. Activity levels did not change significantly. Early caloric increases predicted weight gain at 26 weeks for abstinent women. No relation was found for abstinent men, but interpretation of this finding is weakened by a small subsample size. Abstinent subjects gained over 9 lb by 26 weeks postquit. Despite this gain, Week 26 results showed that caloric intake for abstinent women was approximately equal to that observed at baseline, whereas that for abstinent men had dropped significantly.