Cerebral malaria and epilepsy

Malaria, one of the most common parasitic diseases worldwide, is responsible for more than one million deaths among African children every year. Its neurological form, known as cerebral malaria (CM) is a potential cause of epilepsy in malaria-endemic regions of the world, primarily made up for the most part by the sub-Saharan Africa. Herein, we review recent African studies that examine the association between CM and epilepsy. Three studies suggest a modestly strong association between CM and epilepsy. Furthermore, there appears little doubt that this association is causal. Speculative considerations that may explain this causal association are discussed in this review. Additional research is however required in order to determine the clinical and electrographic behavior, the underlying structural and molecular basis, and course and outcome of this condition.     

Construction of a 28-mm 1H/13C probe and actively shielded Z-gradient set for operation in a 9.4 T/89 mm magnet

In this work, we present a new RF and gradient assembly for operation in a 9.4 Tesla 189 mm magnet. This assembly was designed in order to enable ¹H-NMR perfusion studies that are based on proton-observed carbon-edited approaches or gradient selected double quantum coherence. The RF portion of this probe assembly is comprised of a modified Alderman-Grant coil and a saddle coil operating at 400 and 100 MHz, respectively. These coils are surrounded by an actively shielded Z gradient, which also allows for the use of gradient-based water suppression without the need for carbon selection. We demonstrate that this probe can be used to implement gradient selected double quantum coherence experiments resulting in a high degree of water suppression.     

Risk factors for CD4 lymphopenia in patients treated with a tenofovir/didanosine high dose-containing highly active antiretroviral therapy regimen

In this study, the dynamics of CD4 cell depletion during tenofovir/didanosine co-administration were analysed. Ninety-five HIV-positive patients were followed for 562 days, and 37 lost at least 50 CD4 cells, with a median delay of 274 days. Cox analysis showed that the CD4 cell decrease was associated with a duration of treatment by didanosine of more than 853 days and a didanosine dose of more than 5.50 mg/kg.     

Clinical usefulness of D-dimer depending on clinical probability and cutoff value in outpatients with suspected pulmonary embolism

BACKGROUND: We evaluated whether a highly sensitive D-dimer test is clinically useful and safe for ruling out pulmonary embolism (PE) in patients with a high clinical probability and whether adopting different cutoff values according to the clinical probability category might increase the proportion of patients in whom PE is ruled out. METHODS: We retrospectively analyzed the databases of 2 outcome studies on the diagnosis of PE with a 3-month follow-up that included 1409 patients. We evaluated the usefulness of D-dimer testing by calculating the number needed to test to rule out one PE, and its safety by measuring the 3-month thromboembolic risk in patients not treated by anticoagulant agents based on a normal D-dimer level. RESULTS: The sensitivity of D-dimer was 100% in all clinical probability categories, but the number needed to test increased with increasing clinical probability of PE. The 95% confidence interval (0%-23%) of the 3-month thromboembolic risk (0%) among 13 of 121 patients with a normal D-dimer level and a high clinical probability of PE was wide. Increasing the cutoff value to 700 mug/L in patients with a low clinical probability would rule out PE in an additional 5% of the entire patient cohort at the expense of a lower sensitivity (93% [95% confidence interval, 83%-97%]). CONCLUSIONS: The safety of D-dimer testing in patients with a high clinical probability of PE is not established, and testing results are rarely negative in such patients. Increasing the enzyme-linked immunosorbent assay D-dimer cutoff value only marginally increased the test's usefulness.     

Dynamic 13C NMR analysis of pyruvate and lactate oxidation in the in vivo canine myocardium: Evidence of reduced utilization with increased work

In this work, substrate selection was monitored in the left ventricle of the canine myocardium by following pyruvate and lactate oxidation under in vivo conditions at basal and elevated workloads. These studies were conducted in the open chest model using dynamic ¹³C NMR techniques in the presence and absence of dichloroacetic acid (DCA), a well-known activator of pyruvate dehydrogenase (PDH). Following the infusion of (3-¹³C) pyruvate or (3-¹³C) lactate into the left anterior descending artery, highly variable ¹³C enrichments of glutamate, alanine, aspartate, and citrate were noted under low (RPP <14,500 mmHg/min), intermediate (RPP = 15,000–25,000 mmHg/min), and high (RPP > 25,500 mmHg/min) rate pressure products (RPP). At low workloads, the myocardium typically oxidized the infused (3-¹³C) pyruvate or (3-¹³C) lactate and incorporated the labeled carbon into the glutamate pool as expected. However, in a few notable instances (n = 3), ¹³C-enriched pyruvate and lactate were unable to label the glutamate pool under in vivo conditions even at the lowest RPPs, indicating a lack of selection for these substrates by the tricarboxylic acid (TCA) cycle. Nonetheless, the levels of glutamate C4 enrichment observed at low workloads could usually be enhanced by infusion of DCA. Importantly, ¹³C NMR extract analysis revealed that (3-¹³C) pyruvate or (3-¹³C) lactate labeling of the glutamate pool was reduced (<20%) at high workloads in spite of increased DCA concentrations.     

Transmural metabolite distribution in regional myocardial ischemia as studied with 31P NMR

Phosphorus-31 nuclear magnetic resonance (31P NMR) has been applied to study the canine heart prior to and during regional myocardial ischemia induced by partial flow reduction in the left anterior descending coronary artery (LAD). NMR data were acquired in a transmural fashion by restricting the signal to a column perpendicular to the heart wall using B0 gradients and obtaining spectroscopic spatial resolution along the third dimension using the B1 gradient and adiabatic excitation. With this approach, transmural spectra were accumulated in five separate voxels spanning the wall of the left ventricle from the epicardium to the endocardium. In the normal canine myocardium the levels of high-energy phosphates CP and ATP were relatively constant throughout the left ventricular wall, with only minor evidence of free inorganic phosphate in any of the transmural voxels. However, during sustained partial occlusion of the LAD, significant regional differences between the epi- and the endocardium were noted. The data demonstrate the importance of studying cardiac bioenergetics with transmural differentiation.