Hemolytic uremic syndrome due to an altered factor H triggered by neonatal pertussis

We report on a previously healthy newborn suffering from severe Bordetella pertussis infection who developed hemolytic uremic syndrome (HUS) a few weeks after the onset of whooping cough, with a fatal outcome. A factor H protein with abnormal mobility was found in the serum of the patient as analyzed by Western blotting, indicating that B. pertussis infection might have triggered HUS in a genetically predisposed patient. Received: 13 July 2000 / Revised: 3 October 2001 / Accepted: 9 October 2001     

Dobutamine induces ineffective work in regional ischaemic myocardium: an experimental strain rate imaging study

In the present study, we sought to investigate the effects of differing inotropic conditions on regional myocardial function in ischaemic segments. In an experimental pig model ( n =11), the regional deformation parameters peak systolic strain rate [SR(SYS) (peak velocity of thickening)], systolic strain [epsilon(SYS) (systolic wall thickening)] and post-systolic strain [epsilon(PST) (ongoing wall thickening after end of systole)] were measured during normal perfusion and regional ischaemia of the posterior wall. These parameters were compared with global contractility [E(ES) (end-systolic elastance)] measured by a conductance catheter. Ischaemia was induced by an active coronary hypoperfusion in the circumflex coronary artery. Measurements were done at baseline, during dobutamine and during esmolol infusion. In normal perfused hearts, SR(SYS) (4.8+/-0.2 s(-1) at baseline) increased during dobutamine infusion, decreased during esmolol infusion and correlated significantly with global E(ES). In addition, epsilon(SYS) averaged 93+/-3% at baseline and there was almost no epsilon(PST) (4+/-1%) in normal myocardium. In ischaemic myocardium, SR(SYS) and epsilon(SYS) were significantly reduced compared with normal myocardium at baseline (SR(SYS)=2.8+/-0.3 s(-1), and epsilon(SYS)=43+/-6%; P <0.001 compared with normal perfused hearts), whereas global E(ES) was unchanged. In contrast, epsilon(PST) was significantly increased in regional ischaemic segments compared with the non-ischaemic myocardium (15+/-2%; P <0.001). During the dobutamine infusion, SR(SYS) remained unchanged. In contrast, epsilon(SYS) decreased (25+/-5%; P <0.001) and epsilon(PST) increased (25+/-4%; P <0.05) significantly during dobutamine infusion in ischaemic myocardium. In ischaemic segments, an inotropic stimulation with dobutamine resulted in a shift of strain from systole (epsilon(SYS)) to post-systole (epsilon(PST)). Thus dobutamine induced ineffective myocardial work in ischaemic segments.     

CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study

OBJECTIVE: Treatment with antidepressants is frequently associated with adverse effects or insufficient clinical response. Several antidepressants are metabolized by cytochrome P450 (CYP) 2D6. The activity of this enzyme markedly varies among individuals from poor to ultrarapid metabolism on the basis of the polymorphism of the CYP2D6 gene. This association study investigated whether the CYP2D6 genotype distribution differs from that of the German white population either in patients with marked adverse effects or in nonresponders during treatment with antidepressants metabolized by CYP2D6. METHODS: By use of a retrospective, naturalistic approach, outpatient practices and hospitals in southern Germany were asked to report on patients who either had had adverse drug effects or were nonresponsive during treatment with CYP2D6-dependent antidepressants. CYP2D6 genotyping was performed by a panel of polymerase chain reaction techniques. Poor and intermediate metabolizer alleles, as well as allelic duplications of CYP2D6, were detected. RESULTS: Of 28 patients with adverse effects during treatment with a CYP2D6-dependent antidepressant, 8 (29%) had 2 inactive alleles and thus were poor metabolizers. This is a 4-fold increase as compared with the German population (P <.0001). Amplification of fully functional alleles (associated with ultrarapid metabolism) was found in 3 (19%) of the 16 nonresponders (approximately 5.0-fold higher in nonresponders than in the population) (P =.0012). CONCLUSION: The results suggest that the CYP2D6 genotype is associated with the occurrence of adverse effects and clinical nonresponse in psychiatric patients treated with CYP2D6-dependent antidepressants.     

Endocannabinoid transport tightly controls 2-arachidonoyl glycerol actions in the hippocampus: effects of low temperature and the transport inhibitor AM404

The control of endocannabinoid actions on cortical neurons by a putative carrier-mediated uptake is still poorly understood at the level of synaptic transmission. We investigated the effect of an endocannabinoid, 2-arachidonoyl glycerol (2-AG), on inhibitory postsynaptic currents (IPSCs) in hippocampal slices under physiological conditions, and when uptake was altered by a selective blocker or lower temperature. Bath application of 2-AG (20 micro m) caused a 40% reduction in the amplitude of IPSCs evoked in the perisomatic region of CA1 pyramidal neurons at room temperature; this effect could be blocked by a specific CB(1) receptor antagonist, AM251. By contrast, a smaller (20%) but significant suppression of inhibitory transmission was found by 2-AG at 33-35 degrees C. This reduced blocking effect at physiological temperature could be brought back to 40% by coapplying the endocannabinoid uptake blocker, AM404 (10 or 20 micro m) with 2-AG. In parallel experiments, we measured [(3)H]2-AG uptake at different temperatures in primary cultures prepared from cortical neurons. These data confirmed a striking inhibition of [(3)H]2-AG uptake at room temperature compared with values observed at 37 degrees C. Uptake could be significantly modified by anandamide, 2-AG and AM404, suggesting a common transporter for the two endocannabinoids. These findings together demonstrate the presence of an effective endocannabinoid uptake in cortical neurons, which could considerably alter the spatial and temporal constraints of endocannabinoid signalling at physiological temperature, and which may critically change the interpretation of findings at room temperature.