Fever and evoked potentials in multiple sclerosis

Summary The somatosensory evoked potentials (SEPs) and visual evoked potentials (VEPs) were studied in 19 patients with multiple sclerosis; 17 controls were studied during fever (38.0°–39.7°C) and 2–3 days following return to normal temperature. The latencies of components N₂₀ and P₁₁₄ were measured and specified as abnormal when their value exceeded the standard deviation of the controls by 2.5 times. The corresponding criterion for the evaluation of the amplitude of components N₂₀ and P₁₁₄ was a reduction in amplitude of more than 50%. In the controls fever did not cause significant changes in evoked potentials. On the other hand, patients with multiple sclerosis showed abnormalities in evoked potentials during fever in a greater number of recordings (26 of SEPs and 33 of VEBs) than after return to normal temperature (19 and 27 respectively). In addition, the average latency of components N₂₀ and P₁₁₄ was clearly greater in the patients during fever (N₂₀=29.5±5.2 ms and P₁₁₄=143±18.1 ms) than after return to normal temperature (N₂₀=6.6±3.5 ms and P₁₁₄=134±16 ms). The amplitude of components N₂₀ and P₁₁₄ in patients during fever was clearly smaller than after return to normal temperature. These differences were statistically significant. Finally, in two patients, a decrease was found, during fever, in the conduction velocity of the peripheral somatosensory pathway from the median nerve to the wrist at Erb's point.

---

Zusammenfassung Wir studierten die somatosensorisch evozierten Potentiale (SSEP) sowie die visuell evozierten Potentiale (VEP) bei 19 Patienten mit Multipler Sklerose und 17 Kontrollpersonen. Die somatosensorisch und visuell evozierten Potentiale wurden in beiden Gruppen unter dem Einfluß von Fieber als auch zwei bis drei Tage nach dem Abklingen des Fiebers untersucht.Die Latenzzeit der Komponenten N₂₀ und P₁₁₄ wurde als pathologisch bewertet, wenn ihre Werte 2,5 Standardabweichungen über dem Mittelwert von Normalpersonen lagen.Der entsprechende Maßstab für die Bewertung der Höhe der Komponenten N₂₀ und P₁₁₄ war eine Höheminderung über 50%.Wir fanden, daß Fieber bei den Kontrollpersonen keinen wesentlichen Einfluß auf SSEP und VEP hatte. Bei den MS-Patienten haben wir wesentlich mehr Abnormitäten der SSEP und VEP während des Fiebers (26 SSEP und 33 VEP) als nach dem Abklingen des Fiebers (19 SSEP und 27 VEP).Darüber hinaus war der Mittelwert der Latenzzeit der Komponenten N₂₀ und P₁₁₄ bei den MS-Patienten während des Fiebers höher (N₂₀=29,5±5,2 ms; P₁₁₄=143±18,1 ms) als nach dessen Abklingen (N₂₀=26,6±3,5 ms; P₁₁₄=134±16,8 ms).Abgesehen davon war die Höhe der Komponenten N₂₀ und P₁₁₄ während des Fiebers wesentlich kleiner als nach dem Abklingen des Fiebers.Diese Unterschiede sind statistisch signifikant.Ferner fanden wir während des Fiebers bei zwei Patienten eine Verminderung der Erregungsleitungsgeschwindigkeit im N. medianus zwischen Handgelenk und Erbschen Punkt.

     

Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment

The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.     

Rapid dark aging of biomass burning as an overlooked source of oxidized organic aerosol

Oxidized organic aerosol (OOA) is a major component of ambient particulate matter, substantially impacting climate, human health, and ecosystems. OOA is readily produced in the presence of sunlight, and requires days of photooxidation to reach the levels observed in the atmosphere. High concentrations of OOA are thus expected in the summer; however, our current mechanistic understanding fails to explain elevated OOA during wintertime periods of low photochemical activity that coincide with periods of intense biomass burning. As a result, atmospheric models underpredict OOA concentrations by a factor of 3 to 5. Here we show that fresh emissions from biomass burning exposed to NO₂ and O₃ (precursors to the NO₃ radical) rapidly form OOA in the laboratory over a few hours and without any sunlight. The extent of oxidation is sensitive to relative humidity. The resulting OOA chemical composition is consistent with the observed OOA in field studies in major urban areas. Additionally, this dark chemical processing leads to significant enhancements in secondary nitrate aerosol, of which 50 to 60% is estimated to be organic. Simulations that include this understanding of dark chemical processing show that over 70% of organic aerosol from biomass burning is substantially influenced by dark oxidation. This rapid and extensive dark oxidation elevates the importance of nocturnal chemistry and biomass burning as a global source of OOA.

Highly oxidized organic aerosol (OOA) is a dominant component of particulate matter air pollution globally (1–3); however, sources of OOA remain uncertain, limiting the ability of models to accurately represent OOA and thus predict the associated climate, ecosystem, and health implications (4, 5). The current conceptual model of OOA formation suggests that anthropogenic OOA predominantly originates from the oxidation of volatile (VOCs), intermediate volatility (IVOCs), and semivolatile (SVOCs) organic compounds by the OH radical, resulting in lower-volatility products that condense to the particle phase (6). As the OH radical is formed through photolysis and has a very short atmospheric lifetime [less than a second (7)], this oxidation mechanism only occurs in the presence of sunlight. Further, the time scale for OOA formation through oxidation with OH in models is on the order of a few days (8). While this understanding is sufficient in explaining OOA concentrations in summer or periods with high solar radiation, atmospheric models fail to reproduce the observed concentration of OOA in the ambient atmosphere during winter and low-light conditions (9, 10). Fountoukis et al. (9) found simulated OOA concentrations significantly underestimated in wintertime Paris. Tsimpidi et al. (10) also reported an underprediction of simulated OOA globally in winter, suggesting missing sources of both primary OA (POA) and secondary formation pathways. This underproduction suggests a possible overlooked conversion pathway of organic vapors or particles to OOA that is not accounted for in current chemical transport and climate models.As stricter controls on fossil fuel combustion are implemented, residential biomass burning (BB) as a source of heating or cooking is becoming an increasingly important source of OA in urban environments (1, 11, 12). Further, increasing rates of wildfires from climate change are increasing the frequency of smoke-impacted days in urban areas (12–14). BB emissions include high concentrations of POA, SVOCs, IVOCs, and VOCs (15, 16), thus making BB a key source of OOA. Previous research has focused on quantifying the concentration of OOA formed through photochemical oxidation reactions (i.e., OH) with BB emissions (17, 18). However, oxidation of BB emissions in low or no sunlight is less well understood and is not included in chemical transport models. As opposed to OH, the NO₃ radical is formed through reactions with NO₂ and O₃ and is rapidly lost in the presence of sunlight (19). Thus, the NO₃ radical is only available in significant concentrations at night or other low-light conditions (20, 21). Previous research has established that biogenic VOCs may undergo oxidation at night when mixed with anthropogenic emissions containing NO₂ and O₃ (19, 22–27). There have been only a few studies that consider that nighttime oxidation of residential wood combustion may proceed through similar pathways (28–31); however, the magnitude and relevance to observed OOA in the ambient atmosphere has not yet been established. By combining laboratory experiments and ambient observations to inform a chemical transport model, we present strong evidence that nighttime oxidation of BB plumes (proceeding through reactions with O₃ and the NO₃ radical) is an important source of OOA.     

Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon

BACKGROUND: The development of novel artemisinin-combination therapies suitable for the treatment of pediatric patients suffering from malaria is a research priority. The aim of this study was to investigate a novel fixed-dose pyronaridine-artesunate combination for the treatment of uncomplicated falciparum malaria in Gabonese patients 2-14 years old. METHODS: The study was designed as an open-label dose-escalation study recruiting 60 pediatric patients sequentially in 4 treatment cohorts: study drugs were administered once daily for 3 days, as tablet coformulations (pyronaridine:artesunate ratios of 6:2, 9:3, and 12:4 mg/kg) and as a granule coformulation (pyronaridine:artesunate ratio of 9:3 mg/kg). The primary end points were tolerability, safety, and pharmacokinetics of pyronaridine-artesunate treatment. Efficacy was treated as a secondary outcome measure. RESULTS: The drugs had a good tolerability and safety profile, at all dose levels. Pharmacokinetic analysis revealed a dose-dependent increase in the maximum plasma/blood concentration and the area under the curve, as well as comparable relative bioavailability for the granule coformulation. Polymerase chain reaction-corrected cure rates at day 28 were 100% in per-protocol analysis, at all dose levels. CONCLUSIONS: Pyronaridine-artesunate is a promising novel artemisinin-combination therapy for pediatric patients with uncomplicated Plasmodium falciparum malaria, and the development of both the tablet and the granule coformulations is warranted.     

The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.     

Presence of Cobalt and Chromium Ions in the Seminal Fluid of Young Patients With Metal-on-Metal Total Hip Arthroplasty

We aimed to investigate the effect of metal ions on the semen of males of child fathering age with metal-on-metal (MM) total hip arthroplasty (THA). Semen was collected form 11 patients with MM THA and 5 control of comparable age. Cobalt and chromiun concentrations were measured in both the seminal plasma and in the blood of patients. Results showed that cobalt level was higher in the seminal plasma of MM THA patients (2.89 μg/L) compared to control patients (1.12 μg/L) (P = .011). The ejaculate volume, the sperm density, the total sperm count, the pH, and the percentage of cells with normal morphology were in the range of the World Health Organization criteria for fertile population.     

Laparoscopic adrenalectomy in patients with subclinical Cushing syndrome

Background

Subclinical Cushing syndrome in patients with adrenal incidentalomas has been associated with an increased prevalence of the metabolic syndrome and cardiovascular risk. The management of these patients, be it conservative or surgical, is still debated, but there is accumulating evidence that surgery is best and that laparoscopic adrenalectomy, when possible, is the most preferred procedure. Here we present the short- and long-term results of laparoscopic adrenalectomy for subclinical Cushing syndrome and determine the effect of this procedure on components of the metabolic syndrome.

Methods

Twenty-nine patients, 8 men and 21 women with adrenal incidentalomas and subclinical Cushing syndrome who underwent laparoscopic adrenalectomy, were studied retrospectively. They had undergone postoperative follow-up for improvement or worsening of their arterial blood pressure, body weight, and fasting glucose level for a mean period of 77 months.

Results

Preoperatively, 17 patients (58.6 %) had arterial hypertension, 14 (48.3 %) had a body mass index exceeding 27 kg/m², and 12 (41.4 %) had diabetes mellitus. Postoperatively, a decrease in mean arterial pressure was found in 12 patients (70.6 %), a decrease in body mass index in 6 patients (42.9 %), and an improvement in glycemic control in 5 patients (41.7 %).

Conclusions

Laparoscopic adrenalectomy is beneficial in many patients with subclinical Cushing syndrome because it reduces arterial blood pressure, body weight, and fasting glucose levels. Prospective randomized studies are needed to compare laparoscopic adrenalectomy with a conservative approach and to confirm these results.     

Association between MRI findings and clinical outcomes in a period of 5 years after lumbar spine microdiscectomy

European Journal of Orthopaedic Surgery & Traumatology - To evaluate the associations between magnetic resonance imaging (MRI) findings and pain, disability and quality of life before surgery...