Reflex increases in heart-rate induced by perfusing the hind leg of the rat with solutions containing lactic acid

The hypothesis that metabolic receptors in skeletal muscle influence heart-rate during exercise was tested by means of a perfused preparation of the rat's hind legs. The isolated leg was connected to the body only by nerve and bone and was perfused with tyrode solution. The humoral changes of exercise were simulated by perfusing with modified tyrode solutions in which concentration of K⁺, osmolality, concentrations of lactic acid, and inorganic phosphate were changed to reflect to those occurring during heavy exercise. Only perfusion with a solution enriched with lactic acid elicited a significant increase in heart-rate. The response disappeared when the nerve supply to the leg was cooled or sectioned. 20–60 s after the start of perfusion with solution of high [lactic acid] heart-rate began to increase reaching a maximum ( ± SE = 20.2 ± 8.2,n = 7) after about 2 min. The effect on heart-rate increased when the venous concentration of lactic acid was increased the range from 3 to 10 mmol/l. In further experiments, we tried to separate the effects of pH and lactate. Heart-rate responses were induced only at low pH and at low pH the extent to which heart-rate changed increased with increases in lactate concentration.     

Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC

Objective  

The implementation of NTBC into treatment of hypertyrosinemia type I (HT I) greatly improved survival by prevention of acute liver failure and hepatocellular carcinoma. However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations.     

Mechanisms behind flare of renal lupus during murine pregnancy

The outcome of pregnancy in systemic lupus erythematosus is still controversial. The authors recently reported the disappearance of the manifestation of the skin disease but a diminished survival rate in lupus-prone animals undergoing several pregnancies. It was postulated that lupus-prone animals must have subclinical renal symptoms at an early age and that immune and hormonal changes during pregnancy exacerbate immune reactions in the kidneys, leading to a shortened life span. Here, the authors analysed changes at day 14 of pregnancy in lupus-prone LPR (MRL/lpr) mice and MRL controls regarding cytokines, regulatory T (Treg) cells and deposition of immunocomplexes. Worsened kidney function was observed during pregnancy, even in the absence of lupus signs. This was accompanied by renal inflammation and higher interferon-gamma and interleukin-10 levels. C3 and immunoglobulin G deposition was enhanced in kidney and placenta from lupus-prone pregnant animals. Pregnancy enhanced the levels of Treg cells in control animals but not in lupus-prone animals. As pregnancy-induced Treg cells were shown to be specific for paternal antigens it is not to be expected that these Treg cells can help to destroy autoreactive cells. The authors conclude that early subclinical kidney disease in lupus-prone animals exacerbates during pregnancy. Albeit obtained with an experimental animal model, their data are potentially of importance for lupus patients of reproductive age.     

Differential processing of hierarchical visual stimuli in young and older healthy adults: implications for pathology

Hierarchical figures in which large (global) forms are constructed from smaller (local) forms (Navon, 1977) have proved valuable in studies of perceptual organisation and hemispheric specialisation in both healthy volunteers and a wide range of neurological and psychiatric patients. In studies using Navon figures, normal young adults typically identify global forms faster than local forms. When the global and local forms are incongruent (e.g., a large E made of smaller Rs), global forms often interfere with local form identification more than vice versa. In two conditions on the same subjects, we contrasted the performance of young (mean age 22 years) and older (mean age 58 years) healthy volunteers on global and local processing. In the directed attention task, subjects were instructed to detect a target letter that occurred at the prespecified local or global level. The young subjects showed, as expected, faster reaction times (RTs) to detect global targets. In contrast, the older subjects showed significantly faster RTs to the local targets. Likewise, in a divided attention task, in which subjects were instructed to detect a target letter that could occur at either the local or the global level, the young adults were slightly quicker to detect the global targets and the older subjects were significantly quicker to detect the local targets. Error rates were generally low and there was no significant speed/accuracy trade-off in either condition. The observed local precedence effects in healthy older subjects were unexpected and are discussed in reference to previous work on differential hemispheric aging. That work has suggested that the left hemisphere is preferentially biased toward local processing and ages relatively slowly while the right hemisphere is biased toward global processing and ages relatively quickly. The implications of such putative differential aging for the interpretation of pathological local/global processing in neurological and psychiatric diseases are also emphasised.     

Health-related quality of life in children and adolescents with phenylketonuria: unimpaired HRQoL in patients but feared school failure in parents

Aim of the study was the evaluation of health-related quality of life (HRQoL) and the detection of deviant behavior in early-treated children and adolescents with PKU in comparison with healthy peers. Special focus was laid on the impact of compliance with treatment as defined by the national recommendations on HRQoL. Our investigation in 50 children and adolescents and their parents for the first time demonstrates that despite an overall normal HRQoL in our PKU patient collective, parents are concerned about performance in school especially when phenylalanine concentrations in their children are mainly above the therapeutic range. Adherence to target phenylalanine concentrations ameliorated markedly in patients above 10 years in comparison to younger patients due to relaxed treatment recommendations. Interestingly, this alleged improvement in metabolic control has an impact on the parent assessed but not on the patient assessed appraisal of HRQoL. However, a positive correlation between poor metabolic control and conduct problems was identified by patients’ self-assessment. In conclusion, lacking adherence to the strict treatment recommendations in infancy results in significant concern about school success and success in life in parents of PKU patients. With relaxation of dietary phenylalanine restriction at 10 years of age, these concerns diminish.     

Memory performance in polyvalent MDMA (ecstasy) users who continue or discontinue MDMA use

Background:The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine = MDMA) is a serotonergic neurotoxin in animal studies. Several cross-sectional investigations reported low memory and learning performance in ecstasy users, particularly in those reporting heavy patterns of drug use. Since, serotonin has a recognized role in memory processes, these findings were mostly interpreted as evidence for ecstasy-related neurotoxicity in humans. However, studies with user populations and controls suffer from many inherent methodological problems. Moreover, longitudinal data on memory performance after continued or discontinued ecstasy use are scarce.Methods:In the present longitudinal study, we examined memory performance in 38 MDMA users over the course of 18 months.Results:Subjects who stopped MDMA use after the baseline examination (n = 17) did not improve, and subjects who continued MDMA use (n = 21) did not deteriorate in terms of test performance.Conclusions:Our data do not support, but they also do not rule out memory decline following use of the serotonergic neurotoxin MDMA. In light of the popularity of ecstasy among young people, further investigations are needed. In our view, research strategies should now move to prospective designs in order to shed more light on the course of possible adverse cognitive effects of ecstasy use.     

Directed and divided attention during hierarchical processing in patients with visuo-spatial neglect and matched healthy volunteers

Hierarchically organized figures (for example, a large E made up of smaller N's) are frequently used to investigate directed and divided attention. Investigations of neurological and psychiatric patients, and also tachistoscopic and functional neuroimaging studies on healthy subjects, typically find the right hemisphere to be specialized for the processing of global stimuli and the left hemisphere to be specialized for the processing of local stimuli. In the current study, a group of 12 patients with visuo-spatial neglect (NP) after right hemisphere lesions and 12 age and sex-matched control subjects (CO) performed a directed and a divided attention task with hierarchically organized letters. As expected, faster reaction times were found for control subjects than for neglect patients, especially for the directed global attention task. Lower error rates were found for CO and NP for local than for global targets during the divided attention condition. Local on global interference was found for both groups in reaction times. These local processing advantages for older healthy adults have been reported previously. Additionally, an impairment in the divided attention task was found in both groups, but especially for global targets in NP. This impairment is consistent with other evidence of difficulty in disengaging attention shown by patients with visuo-spatial neglect.     

Advanced Pediatric Neurosonography Techniques: Contrast‐Enhanced Ultrasonography,Elastography, and Beyond

Recent technical advances in neurosonography continue broadening the diagnostic utility, sensitivity, and specificity of ultrasound for detecting intracranial abnormalities bed side. The clinical and functional applications of neurosonography have significantly expanded since the 1980s when transcranial Doppler sonography first allowed anatomic and hemodynamic delineation of the intracranial vessels through the thin temporal skull. In the past few years, contrast‐enhanced ultrasonography, elastography, 3D/4D reconstruction tools, and high‐resolution microvessel imaging techniques have further enhanced the diagnostic significance of neurosonography. Given these advances, a thorough familiarity with these new techniques and devices is crucial for a successful clinical application allowing improved patient care. It is essential that future neurosonography studies compare these advanced techniques against the current “gold standard” computed tomography and magnetic resonance imaging to assure the accuracy of their diagnostic potential. This review will provide a comprehensive update on currently available advanced neurosonography techniques.