bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Plasma Concentration of Serum Amyloid P Component in Centenarians with Impaired Cognitive Performance
Authors: Nybo Mads , Olsen Hanne , Jeune Bernard , Andersen-Ranberg Karen , Holm Nielsen Ellen , Svehag Sven-Erik 
Published: April 2003

Serum amyloid P component (SAP) binds to all amyloid fibrils including those in the plaques and tangles of Alzheimer patients. To investigate whether the plasma SAP concentration correlated to cognitive impairment, we measured SAP levels in blood samples from 41 centenarians and compared these to the cognitive performance evaluated by Mini Mental State Examination (MMSE). We observed a significantly (p < 0.001) increased SAP concentration (48.3 ± 16.9 µg/ml; mean ± SD) in the centenarians compared to gender-matched controls (32.8 ± 11.4 µg/ml). Six severely demented centenarians had an even higher SAP concentration (60.2 µg/ml), while the subgroup of cognitive intact centenarians (MMSE score >24) showed a normal SAP concentration (38.4 ± 9.3 µg/ml). No dehydration or hepatic dysfunction was demonstrable in the centenarians. We conclude that the centenarians with impaired cognitive performance had significantly increased plasma concentrations of SAP, while the values for cognitive intact centenarians were within the normal range.
Intracerebroventricular Infusion of Nerve Growth Factor in Three Patients with Alzheimer’s Disease
Authors: Eriksdotter Jönhagen Maria , Nordberg Agneta , Amberla Kaarina , Bäckman Lars , Ebendal Ted , Meyerson Björn , Olson Lars , Seiger Åke , Shigeta Masahiro , Theodorsson Elvar , Viitanen Matti , Winblad Bengt , Wahlund Lars-Olof 
Published: April 2003

Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer’s disease. We have treated 3 patients with Alzheimer’s disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.
Relatively Preserved Hippocampal Glucose Metabolism in Mild Alzheimer’s Disease
Authors: Ishii Kazunari , Sasaki Masahiro , Yamaji Shigeru , Sakamoto Setsu , Kitagaki Hajime , Mori Etsuro 
Published: April 2003

The purpose of this study was to clarify the changes in hippocampal glucose metabolism in mild Alzheimer’s disease (AD) using positron emission tomography (PET) and 2-(<sup>18</sup>F)fluoro-2-deoxy-<i>D</i>-glucose (FDG). Forty-one patients with probable mild AD (age: 69.0 ± 8.0 years; MMSE: 22.6 ± 2.1) and 22 normal volunteers (age: 67.7 ± 7.1 years) were studied. The regional cerebral metabolic rate for glucose (CMRglc) was measured using FDG and PET. Although the mean CMRglc in the parietal region was significantly lower in the AD group (right: 6.35 ± 1.26 mg/100 g/min; left: 6.37 ± 1.21 mg/100 g/min) than in the control group (right: 7.73 ± 1.02 mg/100 g/min; left: 7.63 ± 0.95 mg/100 g/min), the mean CMRglc in the hippocampus did not show a significant difference between the AD group (right: 4.58 ± 0.70 mg/100 g/min; left: 4.63 ± 0.67 mg/100 g/min) and the control group (right: 5.22 ± 0.65 mg/100 g/min; left: 5.22 ± 0.67 mg/100 g/min) by analysis of variance and post-hoc Tukey’s test. The magnitude of the hippocampal CMRglc reduction was not as large as that of parietal CMRglc reduction. Statistical parametric maps (SPM) analysis also did not significantly demonstrate reduced hippocampal CMRglc in AD patients, although it did show a significant reduction in parietal CMRglc in AD patients. Hippocampal CMRglc was not significantly decreased in mild AD. This was unexpected in view of previous studies that have shown atrophy and clinical dysfunction concerning hippocampus in AD, and suggests that the pathophysiology of the hippocampus in AD may be more complex than was previously thought.
Dehydroepiandrosterone Sulfate Decreases the Interleukin-2-Mediated Overactivity of the Natural Killer Cell Compartment in Senile Dementia of the Alzheimer Type
Authors: Solerte Sebastiano Bruno , Fioravanti Marisa , Schifino Nicola , Cuzzoni Gianni , Fontana Ilaria , Vignati Giulio , Govoni Stefano , Ferrari Ettore 
Published: April 2003

Since dehydroepiandrosterone sulfate (DHEAS) has been involved in the regulation of cellular immunity, the aim of the presence study was to evaluate whether the age-dependent reduction of DHEAS was associated with changes of natural killer (NK) immune function in healthy elderly subjects and in patients with senile dementia of the Alzheimer type (SDAT). Circulating DHEAS was determined throughout 24 h (circadian profile). NK cytotoxic activity was measured as spontaneous and induced cytotoxicity during exposure with DHEAS (10<sup>–7</sup> M), interleukin-2 (IL-2; 100 IU) and IL-2 (100 IU) coincubated with DHEAS (10<sup>–7</sup> M). DHEAS was significantly reduced in healthy elderly subjects (mesor M ± SD = 2.3 ± 0.5 µmol/l) and SDAT (1.6 ± 0.4 µmol/l) patients compared to healthy young subjects (6.7 ± 0.9 µmol/l; p < 0.001); significant differences were also found when healthy elderly subjects and SDAT patients were compared (p < 0.01). A significant inverse correlation between age and DHEAS levels was demonstrated in SDAT and healthy elderly subjects (p < 0.05). The decrease in 24-hour DHEAS secretion was associated with a higher NK cytotoxic response to DHEAS in the healthy elderly subject group than in healthy subjects of young age (p < 0.01). Increased NK cell activity during IL-2 incubation was found in patients with SDAT in comparison with the healthy elderly subject (p < 0.001). On the contrary, NK cell cytotoxic response of SDAT patients was less pronounced during DHEAS exposure and when DHEAS was coincubated with IL-2 (p < 0.001). These data suggest an immunomodulatory role of DHEAS on NK functional activity in physiological aging and SDAT. The antagonizing effect of DHEAS on NK overactivity during exposure with cytokines might counteract some neuroimmune components related to the pathogenesis and progression of the disease.
Absorption of Aluminium-26 in Alzheimer’s Disease, Measured Using Accelerator Mass Spectrometry
Authors: Moore P. Brian , Day J. Philip , Taylor Geoffrey A. , Ferrier I. Nicol , Fifield L. Keith , Edwardson James A. 
Published: April 2003

Although chromosomal abnormalities underpin some early onset cases of familial Alzheimer’s disease (AD), most cases are sporadic and not associated with such abnormalities. Aluminium (Al) is a significant but controversial risk factor for sporadic AD, and studies have reported associations between Al and the principal pathological features of AD, senile plaques and neurofibrillary tangles. The present study measured gastrointestinal (GI) absorption of Al under normal dietary conditions using <sup>26</sup>Al tracer and accelerator mass spectrometry (AMS). Following overnight fast, 13 AD patients (aged 63–76 years) and 13 age-matched controls (aged 62–76 years) ingested a fruit drink containing 27 ng <sup>26</sup>Al. Plasma samples were obtained before and 1 h after the drink and from these the fraction of <sup>26</sup>Al absorbed across the GI tract was estimated. The GI tract rigorously excludes Al with only 0.06–0.1% of the ingested Al being absorbed. The mean fraction absorbed by AD subjects exceeded controls by a factor of 1.64 (p≤0.05, Anova). AMS is capable of determining <10<sup>–16</sup> g of <sup>26</sup>Al with many orders of magnitude more sensitivity than other techniques. Using this sensitivity, we have shown, under normal physiological conditions, that the ability of the GI tract to exclude Al is reduced in AD, possibly leading to greater systemic exposure to Al. Public health measures to limit Al dietary uptake or bioavailability may decrease the prevalence of AD in the community and should be considered.
Medial Temporal Lobe Width on CT Scanning in Alzheimer’s Disease: Comparison with Vascular Dementia, Depression and Dementia with Lewy Bodies
Authors: O’Brien J.T. , Metcalfe S. , Swann A. , Hobson J. , Jobst K. , Ballard C. , McKeith I. , Gholkar A. 
Published: April 2003

A simple linear measurement of the minimum width of the medial temporal lobe (MTL) on angled CT scans has been suggested as an accurate ante-mortem marker for Alzheimer’s disease (AD). To determine the clinical utility and specificity of this finding, we performed angled CT scans with 5-mm slices in 116 subjects referred to a geographically based Old Age Psychiatry service in Newcastle. Diagnoses were of NINCDS/ADRDA AD (n = 69, 36 probable and 33 possible). NINDS/AIREN vascular dementia (VaD, n = 25), consensus criteria for dementia with Lewy bodies (DLB, n = 9) and DSM-IV criteria for major depression (n = 13). Subjects were well matched for age. Minimum MTL width was significantly greater in depressed subjects (13.7 mm) compared to those with dementia, though no differences were seen within the dementia groups (AD 10.8, VaD 10.4, and DLB 10.9 mm). An MTL width below 11.5 mm had a sensitivity of 54% (56/103) and a specificity of 77% (10/13) for distinguishing dementia from depression. We conclude that a single cross-sectional measurement of MTL width on CT does not help differentiate between different types of dementia, though it may provide some supportive evidence when distinguishing depression from dementia.
Dopaminergic and Glutamatergic Interactions in the Expression of Self-Injurious Behavior
Authors: King Bryan H. , Cromwell Howard C. , Lee Hoa T. , Behrstock Soshana P. , Schmanke Troy , Maidment Nigel T. 
Published: April 2003

Self-injurious behavior occurring in persons with severe mental retardation is a clinically significant and poorly understood problem. Multiple neurotransmitter systems have been implicated in the pathogenesis of this behavior, particularly dopaminergic, opioidergic, and serotonergic systems. Pemoline, a central stimulant, administered systemically at high doses reliably produces self-biting behavior in the rat. The systemic bolus of pemoline produces sustained neostriatal levels of pemoline for over 24 h in a continuous infusion paradigm. Studies of the effect of cortical lesions on pemoline-mediated behaviors reveal that cortical damage, as is common in profound mental retardation, lowers the threshold for pemoline-induced self-biting behavior. Data from the corticostriatal slice suggests that sustained exposure to pemoline produces a shift in N-methyl-<i>D</i>-aspartate receptor-mediated responses rendering them more susceptible to dopaminergic enhancement. Thus, dopaminergic and glutamatergic interactions appear to play an important role in the development and expression of self-biting in the pemoline model.
Excitotoxicity and Oxidative Stress during Inhibition of Energy Metabolism
Authors: Zeevalk G.D. , Bernard L.P. , Sinha C. , Ehrhart J. , Nicklas W.J. 
Published: April 2003

Glutamate receptor involvement and oxidative stress have both been implicated in damage to neurons due to impairment of energy metabolism. Using two different neuronal in vitro model systems, an ex vivo chick retinal preparation and dopamine neurons in mesencephalic culture, the involvement and interaction of these events as early occurring contributors to irreversible neuronal damage have been examined. Consistent with previous reports, the early acute changes in the retinal preparation, as well as irreversible loss of dopamine neurons due to inhibition of metabolism, can be prevented by blocking NMDA receptors during the time of energy inhibition. Oxidative stress was suggested to be a downstream consequence and contributor to neuronal cell loss due to either glutamate receptor overstimulation or metabolic inhibition since trapping of free radicals with the cyclic nitrone spin-trapping agent MDL 102,832 (1 m<i>M</i>) attenuated acute excitotoxicity in the retinal preparation or loss of mesencephalic dopamine neurons due to either metabolic inhibition by the succinate dehydrogenase inhibitor, malonate, or exposure to excitotoxins. In mesencephalic culture, malonate caused an enhanced efflux of both oxidized and reduced glutathione into the medium, a significant reduction in total reduced glutathione and a significant increase in total oxidized glutathione at time points that preceded those necessary to cause toxicity. These findings provide direct evidence for early oxidative events occurring following malonate exposure and suggest that the glutathione system is important for protecting neurons during inhibition of energy metabolism. Consistent with this, lowering of glutathione by buthionine sulfoxamine (BSO) pretreatment greatly potentiated malonate toxicity in the mesencephalic dopamine population. In contrast, BSO pretreatment did not potentiate glutamate toxicity. This latter finding indicates dissimilarities in the type of oxidative stress that is generated by the two insults and suggests that the oxidative challenge during energy inhibition is not solely a downstream consequence of glutamate receptor overstimulation.
Hippocampal Sclerosis: Development in Adult Life
Authors: Jackson G.D. , Chambers B.R. , Berkovic S.F. 
Published: April 2003

Hippocampal sclerosis (HS) is the most common pathological lesion underyling intractable temporal lobe epilepsy. It is not known whether HS exists before the onset of epilepsy or whether it is caused by seizures. Its has been proposed that childhood seizures cause HS. Optimized magnetic resonance imaging (MRI), hippocampal volumes and T<sub>2</sub> signal quantitation were performed 2 weeks and 8 months following at tonic-clonic seizure in a 23-year-old man. MRI 14 days after the seizure showed symmetrical hippocampal volumes (ratio R/L = 1.03) with intact internal architecture bilaterally but marked signal change in the right hippocampus (T<sub>2</sub> right = 121, T<sub>2</sub> left = 103, normal ≤108 ms). Eight months later this hippocampus showed severe atrophy with a volume ratio of 0.65 and T<sub>2</sub> values of 117 (right) and 109 ms (left). High-resolution imaging showed that volume loss occurred mainly in the CA1 region which showed high signal in the initial study. Characteristic MRI features of HS can develop in adults and HS cannot always be assumed to have its origins in childhood. Hypoxia in the context of seizures may be an important component in hippocampal damage. HS may be a preventable lesion and MRI signal change seen in the neuronal layers of the hippocampus may be an indication for neuroprotection.
Noggin Is a Negative Regulator of Neuronal Differentiation in Developing Neocortex
Authors: Li Weiwei , LoTurco Joseph J. 
Published: April 2003

Bone morphogenetic proteins (BMPs) trigger neuronal differentiation of neocortical precursors within the ventricular zone (VZ) [Li et al. (1998): J Neurosci 18:8853–8862]. BMP-2/4 protein is concentrated at the VZ surface and BMPs rapidly promote the differentiation of neocortical precursors in both dissociated cell and explant cultures. Noggin binds to BMP-2/4 with high affinity, and prevents binding to cell surface receptors. In the present study, we used human recombinant noggin protein to determine whether endogenous BMP-2/4 triggers neuronal differentiation in dissociated cell culture. We find that noggin inhibits the differentiation of neocortical neurons: noggin decreases the number of MAP-2- and TUJ1-positive cells after 24 h of treatment, yet has no effect on either proliferation or cell survival. Noggin also significantly decreases neurite growth of MAP-2-positive cells. In addition, using Western blot analysis we show that noggin protein is present in developing cortex at E15. These results are consistent with previous results showing that endogenous BMPs trigger neuronal differentiation in the neocortical VZ and also indicate that a balance of noggin and BMP may regulate the differentiation of neocortical neurons in vivo.
Instrumental Measurement of the Mantoux Test: Differential Effects of Tuberculin and Sodium Lauryl Sulphate on Impedance Response Patterns in Human Skin
Authors: Nyrén Miruna , Hagströmer Lena , Emtestam Lennart 
Published: April 2003

<i>Background and Objective:</i> The tuberculin (PPD) test is a model reaction for the cell-mediated immune system of the skin. The aim of this study is to compare the non-invasive technique based on electrical impedance for investigation of the tuberculin test with an irritant contact reaction induced by sodium lauryl sulphate, which has already been carefully evaluated using this method. <i>Methods:</i> 0.1 ml of PPD (2 TU) was injected intracutaneously into the volar forearms of 20 adult healthy subjects, all known to be tuberculin sensitized. Assessments were performed 3 and 7 days after the injections, using visual scoring, a new electrical impedance technique and transepidermal water loss (TEWL). <i>Results:</i> In the 16 cases that completed the study, compared to relevant controls and reactions induced by sodium lauryl sulphate statistically significant changes in 3 of the 4 impedance indices were found: both the means of index MIX and index IMIX increased (p ≤ 0.01) and the mean of index PIX decreased (p ≤ 0.05). Furthermore, similar impedance response patterns occurred in another cell- mediated immune reaction that we have studied previously – namely, the allergic contact reaction induced by nickel sulphate. Unlike the irritant reactions, no significant increase in TEWL values in tuberculin reactions were found. This can be explained by the fact that the epidermis is little affected, since the inflammatory process in the tuberculin reaction is located more deeply in the dermis than with the irritant reaction. <i>Conclusion:</i> The current study strongly indicates that electrical impedance in the described version, besides contact dermatitis, also seems suitable for studies of the tuberculin reaction. This will add a new indication for the technique, and studies of further clinical applications are in progress.
Preoperative ERCP Approach to Common Bile Duct Stones:Results of a Selective Policy
Authors: Rijna H. , Kemps W.G.M. , Eijsbouts Q. , Meuwissen S.G.M. , Cuesta M.A. 
Published: April 2003

<i>Background:</i> In a previous study, we made a plea for more selective indications for preoperative ERCP in patients with gallstones based on the results obtained from a liberal policy. Following 3.5 years of implementing this selective policy, a report on the results are presented here. This study was performed in a referral academic hospital. <i>Methods:</i> Between June 1994 and December 1997, 328 patients underwent cholecystectomy because of symptomatic cholelithiasis. Absolute indications for preoperative ERCP were: acute cholangitis (4 patients); obstructive jaundice (22 patients); gallstone pancreatitis (within the first 24 h in 14 patients), and wide common bile duct (CBD, >8 mm) with suspicion of stones in the biliary tree (2 patients). <i>Results:</i> In 42 patients (12.8%) a preoperative ERCP was performed for these indications. Stones were found in the CBD in 30 patients and edema in the papilla in 2 patients (total 76.2%). The stones could be extracted by endoscopic sphincterotomy in 24 of the 30 patients (80%). Complications were seen in 7 patients (16.7%). All these complications (bleeding of the papilla in 4 and mild pancreatitis in 3 patients) could be treated conservatively. During a mean follow-up of 2.5 years, CBD stones could be demonstrated postoperatively in 3 patients (0.3%). No mortality was observed in this series. <i>Conclusions: </i>The results of this selective policy included the expected outcome of a significant reduction in the number of ERCPs performed from 29 to 12.8% (p < 0.001, χ<sup>2</sup> test) and a better yield of stones, from 29 to 76.2% of the patients. The mortality of the procedure decreased from 2 to 0% whereas morbidity remained the same. This selective policy seems adequate for the preoperative assessment of CBD stones.
Long-Term Results of Anterior Anal Sphincter Repair for Fecal Incontinence due to Obstetric Injury / with Invited Commentaries
Authors: Rothbarth J. , Bemelman W.A. , Meijerink W.J.H.J. , Buyze-Westerweel M.E. , van Dijk J.G. , Delemarre J.B.V.M. 
Published: April 2003

<i>Aims:</i> This study is to report short- and long-term results of anterior sphincter repair for fecal incontinence due to obstetric injury and factors predicting an unsuccessful outcome. <i>Methods:</i> Thirty-nine consecutive patients, mean age 51 years (range 29–74), who underwent anterior sphincter repair for fecal incontinence due to obstetric injury were investigated. Duration of symptoms ranged from 9 months to 34 years. All patients underwent an anterior overlapping sphincter muscle reconstruction and in most cases a puborectal muscle plasty. <i>Results:</i> Three months after surgery 77% of the patients had regained continence (Parks score of 1 or 2), at 9 months 67% were continent and after 12 months or more (mean, range 12–114) only 62%. Patients with prolonged pudendal latency (>2.2 ms) did significantly worse than patients without it (p < 0.05). Patients who had had lateral episiotomy during labor had significantly better outcome than those without it (p < 0.05). <i>Conclusion:</i> The outcome of anterior sphincter repair deteriorates with time after surgery. Assessment should be done at least 1 year after surgery to evaluate the final results of anterior sphincter repair. Prolonged pudendal latency predicts a poor outcome of anterior sphincter repair, and a prior lateral episiotomy is possibly a good prognostic factor.