The importance of choline and different serum parameters for the course of the anorexia nervosa

Malnutrition in anorexia nervosa was simulated in an animal starvation study. Female rats aged 11 to 13 weeks received a hypocaloric standard diet or a hypocaloric choline reduced diet. Weight reduction lasted for 12 to 20 weeks and was between 30 % to 40 % of initial weight. Several animals were refed after weight reduction up to 6 to 12 weeks with a standard or a choline enriched diet ad libitum. Serum parameters and membrane fluidity of the CNS were measured after weight reduction or after refeeding. Weight reduction leads to a significant decrease of serum protein, triglycerides (Z = -3.53 resp. -3.42; p < 0.001) and an increase of membrane fluidity in the CNS (Z = -2.83; p < 0.001). Long-term diet with marked weight reduction and following refeeding causes a catabole metabolic situation with significant increase of urea/creatinine-ratio. Choline enriched refeeding after diet results in normalization of serum parameters and membrane fluidity of the CNS. Choline enrichment leads to a significant increase of serum protein (Z = -2.03; p < 0.01). Besides we found a negative correlation between serum protein and urea/creatinine-ratio (r (S) = -0.47; p < 0.001; n = 64). This is possibly caused by a reduced protein catabolism or an increased protein anabolism. Furthermore membrane fluidity in the CNS correlates with serum protein (r (S) = 0.65; p < 0.001; n = 41) and with serum creatinine levels (r (S) = 0.58; p < 0.001; n = 42). We conclude that these serum parameters are potential predictors for cell function in the starved brain and consequently for the course of anorexia nervosa. We furthermore hypothesize that choline enriched nutrition after starvation improves the stabilization of cerebral membranes and the metabolic situation in anorexia nervosa.     

Successful intravenous thrombolysis for acute stroke in a child

We report an 8-year-old white girl with no previous medical history who developed sudden onset right hemiplegia, left gaze preference, and global aphasia. An acute left middle cerebral artery stroke syndrome was diagnosed. She was treated with intravenous recombinant tissue plasminogen activator, 2 hours after the onset of symptoms. A magnetic resonance image demonstrated an acute left middle cerebral artery stroke, and a magnetic resonance angiography showed a patent left middle cerebral artery. At discharge, she was able to speak normally and walk without support. She was also able to raise the right arm up to the level of the shoulder and showed increased motility of the hand and fingers. No treatment-related complications happened. To the best of our knowledge, this is, so far, the youngest child successfully treated with intravenous recombinant tissue plasminogen activator for acute ischemic stroke.     

Local field potentials and spikes in the human medial temporal lobe are selective to image category

Local field potentials (LFPs) reflect the averaged dendrosomatic activity of synaptic signals of large neuronal populations. In this study, we investigate the selectivity of LFPs and single neuron activity to semantic categories of visual stimuli in the medial temporal lobe of nine neurosurgical patients implanted with intracranial depth electrodes for clinical reasons. Strong selectivity to the category of presented images was found for the amplitude of LFPs in 8% of implanted microelectrodes and for the firing rates of single and multiunits in 14% of microelectrodes. There was little overlap between the LFP- and spike-selective microelectrodes. Separate analysis of the power and phase of LFPs revealed that the mean phase was category-selective around the theta frequency range and that the power of the LFPs was category-selective for high frequencies around the gamma rhythm. Of the 36 microelectrodes with amplitude-selective LFPs, 30 were found in the hippocampus. Finally, it was possible to readout information about the category of stimuli presented to the patients with both spikes and LFPs. Combining spiking and LFP activity enhanced the decoding accuracy in comparison with the accuracy obtained with each signal alone, especially for short time intervals.     

White matter abnormalities and brain activation in schizophrenia: a combined DTI and fMRI study

Diffusion tensor imaging (DTI) studies of schizophrenia have revealed white matter abnormalities in several areas of the brain. The functional impact on either psychopathology or cognition remains, however, poorly understood. Here we analysed both functional MRI (during a working memory task) and DTI data sets in 18 patients with schizophrenia and 18 controls. Firstly, DTI analyses revealed reductions of fractional anisotropy (FA) in the right medial temporal lobe adjacent to the right parahippocampal gyrus, likely to contain fibres of the inferior cingulum bundle, and in the right frontal lobe. Secondly, functional MRI revealed prefrontal, superior parietal and occipital relative hypoactivation in patients with the main effect of task. This was accounted for by reduced prefrontal activation during the encoding phase of the task, but not during maintenance or retrieval phases. Thirdly, we found a direct correlation in patients between the frontal FA reduction (but not medial temporal reductions) and fMRI activation in regions in the prefrontal and occipital cortex. Our study combining fMRI and DTI thus demonstrates altered structure-function relationships in schizophrenia. It highlights a potential relationship between anatomical changes in a frontal-temporal anatomical circuit and functional alterations in the prefrontal cortex.     

Risk of Aspiration Pneumonia in Suspected Variceal Hemorrhage: The Value of Prophylactic Endotracheal Intubation Prior to Endoscopy

Variceal hemorrhage (VH) is a lethal complication of portal hypertension. Aspiration occurring during endoscopic intervention for acute VH is a concern; however, few data exist regarding the efficacy of prophylactic intubation to prevent aspiration pneumonia. We reviewed all endoscopic procedures for acute VH from January 1995 to December 2002; only patients with the absence of hepatic encephalopathy greater than stage II and normal chest x-ray at admission were included. The use of prophylactic intubation, postprocedure chest x-ray, and mortality were recorded. Sixty-two patients (69 bleeding episodes) were identified. Elective intubation was performed in 42 patients (47 episodes); pulmonary infiltrates developed in 7 of 42 (17%), with an overall mortality rate of 9 of 42 (21%). Twenty patients (22 episodes) were not intubated. None developed pulmonary infiltrates, and the overall mortality rate was 1 in 20 (5%). We conclude that in patients with suspected variceal bleeding, elective intubation is associated with a substantial risk of aspiration pneumonia.     

The shifting baseline of northern fur seal ecology in the northeast Pacific Ocean

Historical data provide a baseline against which to judge the significance of recent ecological shifts and guide conservation strategies, especially for species decimated by pre-20th century harvesting. Northern fur seals (NFS; Callorhinus ursinus) are a common pinniped species in archaeological sites from southern California to the Aleutian Islands, yet today they breed almost exclusively on offshore islands at high latitudes. Harvest profiles from archaeological sites contain many unweaned pups, confirming the presence of temperate-latitude breeding colonies in California, the Pacific Northwest, and the eastern Aleutian Islands. Isotopic results suggest that prehistoric NFS fed offshore across their entire range, that California populations were distinct from populations to the north, and that populations breeding at temperate latitudes in the past used a different reproductive strategy than modern populations. The extinction of temperate-latitude breeding populations was asynchronous geographically. In southern California, the Pacific Northwest, and the eastern Aleutians, NFS remained abundant in the archaeological record up to the historical period approximately 200 years B.P.; thus their regional collapse is plausibly attributed to historical hunting or some other anthropogenic ecosystem disturbance. In contrast, NFS populations in central and northern California collapsed at approximately 800 years B.P., long before European contact. The relative roles of human hunting versus climatic factors in explaining this ecological shift are unclear, as more paleoclimate information is needed from the coastal zone.     

Effects of montelukast treatment and withdrawal on fractional exhaled nitric oxide and lung function in children with asthma

BACKGROUND: Leukotriene receptor antagonists (LTRAs) reduce fractional exhaled nitric oxide (Feno) concentrations in children with asthma, but the effect of LTRA withdrawal on Feno and lung function is unknown. We aimed to study the effect of treatment and withdrawal of montelukast, a LTRA, on airway inflammation as reflected by Feno and lung function in children with asthma. METHODS: A double-blind, randomized, placebo controlled, parallel group study was undertaken in 14 atopic children with mild persistent asthma who were treated with oral montelukast (5 mg/d for 4 weeks) and 12 atopic children with mild persistent asthma who received matching placebo. A follow-up visit was performed 2 weeks after montelukast or placebo withdrawal. RESULTS: Montelukast reduced Feno concentrations by 17% (p = 0.067), an effect that was more pronounced (35%) [p = 0.0029] when children with seasonal atopy who were exposed to relevant allergens during the treatment phase were excluded from analysis (n = 3). Compared to those at the end of treatment, Feno concentrations were increased 2 weeks after montelukast withdrawal (p = 0.023) concomitant with a reduction in absolute FEV(1) values (p = 0.011), FEV(1) percentage of predicted values (p = 0.006), FEV(1)/FVC ratio (p = 0.002), and forced expiratory flow at 25% to 75% of FVC values (p = 0.021). These changes were not observed in the placebo group. CONCLUSIONS: LTRAs reduce Feno concentrations in children with asthma, and withdrawal can result in increased Feno values and worsening of lung function in children with asthma.     

Atrial natriuretic peptide, a regulator of nuclear factor-kappaB activation in vivo

Natriuretic peptides (NPs) comprise a family of vasoactive hormones that play important roles in the regulation of cardiovascular and renal homeostasis. Along this line, atrial NP (ANP) (international non-proprietary name: carperitide, HANP) is an approved drug for the treatment of acute heart failure. In recent years, evidence has been given that the NP system possesses a far broader biological spectrum than the regulation of blood pressure and volume homeostasis. In fact, a substantial amount of in vitro work indicates that ANP affects important inflammatory processes and signaling pathways. Quite surprisingly, however, no information exists on the in vivo antiinflammatory potential and signaling of ANP. We show here that pretreatment of lipopolysaccharide (Salmonella abortus equi, 2.5 mg/kg)-challenged mice with ANP (5 microg/kg iv, 15 min) rapidly inhibits nuclear factor-kappaB activation via inhibition of phosphorylation and degradation of the IkappaB-alpha protein. ANP also reduces Akt activation upon lipopolysaccharide injection. In ANP-pretreated mice, the increase of TNF-alpha serum concentration is markedly prevented; most importantly, the survival of these animals improved. These findings demonstrate both in vitro and in vivo an antiinflammatory profile of ANP that deserves to be further investigated in a therapeutic perspective.     

Prolonged survival of porcine hepatocytes in cynomolgus monkeys

BACKGROUND & AIMS: Management of patients with liver failure can be a significant medical challenge, and transplantation of the liver is the only definitive therapy. Whole liver allotransplantation is limited by a shortage of human donors and the risks of the surgery in those most ill. Transplants consisting of xenogeneic hepatocytes might overcome these problems, and work in rodents indicates that such transplants can correct some metabolic deficiencies and can prevent the complications and mortality associated with hepatic failure. As a prelude to clinical application, we tested the feasibility of hepatocyte xenotransplantation in nonhuman primates. METHODS: One to 2 billion hepatocytes from outbred swine were transplanted into the spleens of cynomolgus monkeys using conventional immunosuppression to control rejection. Duration of graft function was determined based on assay for porcine albumin. RESULTS: Following a single infusion, xenogeneic hepatocytes functioned for more than 80 days and, following re-transplantation, for more than 253 days. Engraftment in the spleen was confirmed 40 days after transplantation by asialoglycoprotein receptor-directed nuclear scanning. The humoral immune response to the transplanted porcine cells had no discernible impact on the survival of the grafts. CONCLUSIONS: Xenotransplantation of hepatocytes should be explored as a readily available, minimally invasive form of therapy for hepatic failure.