Visual information is conducted by two parallel pathways (luminance- and contour-processing pathways) which are thought to be differentially affected in migraine and can be investigated by means of pattern-reversal visual evoked potentials (VEPs). Components and habituation of VEPs at four spatial frequencies were compared between 26 migraineurs (13 without aura, MO; 13 with aura, MA) and 28 healthy volunteers. Migraineurs were recorded in the headache-free interval (at least 72 h before and after an attack). Five blocks of 50 responses to chequerboards of 0.5, 1, 2 and 4 cycles per degree (c.p.d.) were sequentially averaged and analysed for latency and amplitude. Differences in VEPs were dependent on spatial frequency. Only when small checks were presented, i.e. at high spatial frequency (2 and 4 c.p.d.), was the latency of N2 significantly prolonged in MA and did it tend to be delayed in MO subjects. Habituation behaviour was not significantly different between groups under the stimulating conditions employed. Prolonged N2 latency might be explained by the lack or attenuation of a contour-specific component N130 in migraineurs, indicating an imbalance of the two visual pathways with relative predominance of the luminance-processing Y system. These results reflect an interictally persisting dysfunction of precortical visual processing which might be relevant in the pathophysiology of migraine.

Psychiatric co-morbidity is an important risk factor for chronification of primary headache into adulthood. The aim of this study was to investigate the extent and clinical relevance of emotional and behavioural problems in children and adolescents with primary headache. Children and adolescents (n = 128) with primary headache (International Headache Society, codes 1.1, 1.2, 2.1) and 83 matched controls aged 6-18 years were examined by standardized dimensional psychometric tests (Child Behaviour Checklist, Depression Inventory for Children and Adolescents, Anxiety Questionnaire for Pupils). Children and adolescents with primary headache suffer more often from internalizing problems (depression, anxiety, somatization) than healthy controls. The detected emotional and behavioural problems are clinically relevant and require particular therapy in every third child suffering from headache. Two out of three children and adolescents with primary headache do not show clinically relevant psychopathology and may benefit from minimal therapeutic intervention. One of three examined headache patients needs additional psychiatric therapy.

The pharmacokinetics of imipenem-cilastatin were investigated in 12 critically ill patients with acute renal failure (ARF) managed by continuous veno-venous hemofiltration (CVVH) while receiving a fixed combination of 500 mg of imipenem-cilastatin intravenously three or four times daily. No adverse drug reactions were observed. Plasma and hemofiltrate samples were taken at specified times during one dosing interval, and the concentrations of imipenem and cilastatin were determined by high-performance liquid chromatography. Pharmacokinetic variables were calculated by a first-order, two-compartment pharmacokinetic model for both substances. Total clearances of imipenem and cilastatin (mean ؎ standard deviations) were 122.2 ؎ 28.6 and 29.2 ؎ 13.7 ml/min, respectively, with hemofiltration clearances of 22.9 ؎ 2.5 and 16.1 ؎ 3.1 ml/min, respectively, and nonrenal, nonhemofiltration clearances of 90.8 ؎ 26.3 and 13.2 ؎ 13.9 ml/min, respectively. Mean imipenem dosage requirements were approximately 2,000 mg/24 h (2,111.8 ؎ 493.4 mg/24 h). They were calculated in order to achieve an average steady-state concentration of 12 mg/liter to ensure that concentrations in plasma exceeded the MICs at which 90% of intermediately resistent bacteria are inhibited (8 mg/liter) during the majority of the dosing interval. By contrast, the recommended dosage for patients with end-stage renal failure (ESRF) and infections caused by intermediately resistant bacteria is 1,000 mg/24 h. This remarkable difference may be due (i) to differences in the nonrenal clearance of imipenem between patients with ARF and ESRF and (ii) to the additional clearance by the hemofilter. Since the total clearance of cilastatin was low, marked accumulation occurred, and this was particularly pronounced in patients with additional liver dysfunction. Thus, in patients with ARF managed by CVVH, rather high imipenem doses are required, and these inevitably result in a marked accumulation of cilastatin. The doses of imipenem recommended for patients with ESRF, however, will lead to underdosing and inadequate antibiotic therapy.

These results suggest that, if target tissue concentrations correlate directly with the degree of pain relief, patients with pain caused by dermal or subcutaneous tissue damage will have greater pain relief after topical administration of ibuprofen accompanied with less systemic side effects. In addition, a proportion of patients with muscle pain may also experience pain relief from topical ibuprofen.