Syntactic language processing: ERP lesion data on the role of the basal ganglia.

The role of the basal ganglia in syntactic language processing was investigated with event-related brain potentials in fourteen neurologically impaired patients. Seven of these patients had basal ganglia lesions while 7 other patients primarily had lesions of the left temporo-parietal region excluding the basal ganglia. All patients listened to sentences that were either correct or included a verb argument structure violation. In previous experiments this type of violation elicited a biphasic pattern of an N400-P600 complex in young healthy participants. While the N400 may result from incorrect semantic-thematic role assignment, the P600 reflects the fact that verb information does not license the syntactic structure at present. Results of the patient experiment revealed a double dissociation: patients with left temporo-parietal lesions only show a P600, whereas patients with lesions of the basal ganglia showed no P600, but a negativity with extended duration that resembled an N400. The latter pattern not only confirms previous reports that the basal ganglia modulate the P600 but extends these results by showing that the N400 as a late semantic-thematic integration process appears partially modulated by the basal ganglia.     

Transferrin Phenotype and Level of Carbohydrate-deficient Transferrin in Healthy Individuals

Elevated concentrations of carbohydrate-deficient components of transferrin (CDT) in serum may be used as a sensitive and specific marker of regular, high alcohol consumption. When determined by a new, simplified assay, CDT values are nearly normally distributed in low- or non-alcohol-consuming control populations. The importance of transferrin phenotype for this normal variation was analyzed in 100 healthy, European men and women with no or negligible alcohol intake. No significant relation was found between phenotype and CDT value in this population. The three rare B-variants found had low CDT levels, and one subject, examined outside the study, with a rare D-variant indicated that D-variants may result in false-positive CDT values. Moreover, women tended to have somewhat higher values than men, in whom CDT levels were weakly correlated with age. Other as yet undefined biological factors are clearly responsible for the major part of the normal variation of CDT values in nonalcoholic individuals.     

A new immune-competent animal model of mucosally derived squamous cell carcinoma.

OBJECTIVES: To develop an immune-competent animal model for mucosally derived squamous cell carcinoma (SCCA). STUDY DESIGN: Fifteen Fischer 344 rats were inoculated with 1, 2, 5, 10, or 20 x 10(6) FAT7 cells in their flanks. The animals were observed for tumor growth and metastasis. RESULTS: All animals developed tumors that grew exponentially. Pulmonary metastases developed in all animals and 13% developed lymph node metastases. CONCLUSION: The FAT7 flank tumor in Fischer 344 rats is a new animal model that closely resembles the behavior of human mucosal head and neck cancer. SIGNIFICANCE: The existence of an immune-competent, mucosally derived, and reliable animal model of SCCA that somewhat resembles human head and neck SCCA gives the opportunity to perform immune-modulating experiments on head and neck cancer in these animals. EBM rating: B-3.     

The economics of general thromboembolic prophylaxis

The clinical and economic effects of each of 3 alternatives—no prophylaxis, general prophylaxis, and selective treatment—have been assessed in conjunction with 3 types of surgery—general surgery, the subset surgery for cholelithiasis, and elective hip surgery. The costs of thromboembolic and hemorrhagic complications have been calculated from the figures for 28 patients hospitalized at the Department of Surgery, Malmö General Hospital, Malmö, Sweden. The anticipated number of thromboembolic complications—and thus even the number of fatal pulmonary embolisms—can be minimized in all 3 types of surgery by means of general prophylaxis. General prophylaxis with low-dose heparin is, however, accompanied by the greatest incidence of hemorrhagic complications. Health care costs are minimized with general prophylaxis in elective hip and general surgery, while no prophylaxis is the best alternative in surgery for cholelithiasis. From the patient's point of view, general prophylaxis minimizes the duration of thromboembolic disease in general surgery as well as in elective hip surgery. In surgery for cholelithiasis, however, no differences in health loss for the individual are shown between the 2 main alternatives, no prophylaxis and general prophylaxis. Selective treatment means treatment after diagnosis of thrombosis with some screening method. The alternative selective treatment was the least satisfactory of those 3 studied.

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Resumen Los efectos clínicos y económicos de cada una de 3 alternatives en la profilaxis tromboembólica (no profilaxis, profilaxis general con heparina de baja dosis, y tratamiento selectivo) fueron valorados en 3 tipos de cirugía: cirugía general (abdominal), el subgrupo de cirugía general para colelitiasis, y cirugía electiva de cadera. Los costos de las complicaciones tromboembólicas y hemorrágicas fueron calculados a partir de las cifras observadas en 28 pacientes hospitalizados en el Departmento de Cirugía. El número de predicción de complicaciones tromboembólicas, y el número de embolismos pulmonares fatales pueden ser minimizados en los 3 tipos de cirugía mediante la profilaxis general. Sin embargo, la profilaxis general con heparina de baja dosis se acompaña de la más alta incidencia de complicaciones hemorrágicas.Los costos de la atención pueden ser minimizados mediante la profilaxis general en cirugía electiva de cadera y en cirugía general abdominal, en tanto que la no profilaxis es la mejor alternativa para la cirugía de colelitiasis.Desde el punto de vista del paciente, la profilaxis general minimiza la duración de la enfermedad tromboembólica en la cirugía general abdominal así como en la cirugía electiva de cadera. En la cirugía para colelitiasis, sin embargo, no se demuestran diferencias entre las dos alternatives principales, no profilaxis y profilaxis general.El tratamiento selectivo significa tratamiento una vez establecido el diagnóstico de trombosis mediante algún método de tamizaje. La alternativa de tratamiento selectivo fue la menos satisfactoria de las 3 alternatives estudiadas.

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Résumé Les effets cliniques et financiers de 3 comportements variables: absence de prophylaxie, prophylaxie, traitement sélectif ont été évalué en fonction de trois types de chirurgie: chirurgie générale, chirurgie spéciale de la lithiase biliaire, chirurgie élective de la hanche. Les coûts des complications thrombo-emboliques et hémorragiques ont été calculés à partir des données numériques concernant 28 malades hospitalisés dans le service de chirurgie. Le nombre envisagé des complications thromboemboliques et par conséquent le nombre d'embolie pulmonaire fatale a été réduit dans les 3 types de chirurgie choisis grâce au traitement prophylactique. Cependant il convient de noter que le traitement prophylactique à l'aide de faible dose d'héparine s'accompagne de complications hémorragiques plus nombreuses.Les coûts des soins de la chirurgie élective de la hanche et de la chirurgie générale sont réduits grâce au traitement prophylactique alors que l'absence de traitement prophylactique représente la meilleure modalité à observer dans le traitement de la chirurgie biliaire.En ce qui concerne le point de vue du malade le traitement prophylactique réduit la durée de la maladie thromboembolique compliquant la chirurgie générale ou la chirurgie de la hanche. En revanche dans la chirurgie de la lithiase biliaire aucun inconvénient pour la santé du malade ne s'observe que le traitement prophylactique soit ou ne soit pas appliqué.Le traitement sélectif qui répond au traitement institué après que le diagnostic ait été posé par des méthodes de dépistage est la moins satisfaisante des trois attitudes envisagées.

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Supported by grant no. 00759 from the Swedish Medical Research Council.     

Multiple ionic mechanisms are activated by the potent agonist quisqualate in cultured cerebellar Purkinje neurons.

Current clamp recordings were used to analyze responses of cultured cerebellar Purkinje neurons to quisqualate and several other selective non-N-methyl- D-aspertate (NMDA) agonists. Quisqualate, a potent agonist in the cerebellar Purkinje neuron, evoked both short- and long-term changes in excitability, that activated within seconds and lasted for several minutes. Two components of the response were activated differentially by subtype selective agonists, and differed in their mechanism of expression and time course. The initial component of the response was activated by ionotropic agonists ((RS)-d-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) domoate), and by quisqualate and glutamate which are effective at both the ionotropic and metabotropic quisqualate receptor subtypes, but not by the metabotropic agonist trans (+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD). This component was dependent on extracellular Na+, and characterized by a rapid depolarization with a short latency (less than 1-2 s) and a decrease in membrane resistance as expected for an ionotropic reponse. The rapid depolarization extended into an agonist-dependent plateau phase, which could not be evoked by depolarization alone. The second ('late') phase of the response was a slowly-activating, long-lasting change in membrane excitability, accompanied by little or no change in the membrane potential. The late phase, marked by an increase in voltage-dependent bursting spike activity, was induced by the metabotropic agonist, ACPD, and by quisqualate and glutamate, but not by ionotropic selective agonists such as AMPA. Little or no bursting was evoked by AMPA, domoate, kainate or homocysteate. This late phase was also accompanied by increases in the magnitude and duration of the complex spikes and in the afterhyperpolarization following brief current-driven depolarizations. The slower time course of the late component is consistent with a pathway involving second messenger systems. Our results support the hypothesis that coregulation of both ionotropic and metabotropic mechanisms produces the complex and prolonged excitatory response characteristic of the Purkinje neuron.     

Saturation analysis of specific 11C Ro 15-1788 binding to the human neocortex using positron emission tomography

The ¹¹C-labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand-reduced ¹¹C-flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor-poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density (B_max) and equilibrium dissociation constant (K_d) values on the basis of certain assumptions B_max values were in the order of 90 pmol/g and K_d values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that ¹¹C-flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors.     

Blood pressure reduction in pregnancy by sodium chloride.

Volume expansion in the presence of elevated aldosterone availabilityis a hallmark of normal pregnancy. Intravascular volume depletioncharacterizes severe pregnancy-associated disease conditionssuch as intra-uterine growth retardation, chronic hypertensionor pre-eclampsia [1]. Two hypotheses have been forwarded toexplain volume depletion in pregnancy: the first hypothesischarges inappropriate sensing of vascular ‘overfilling’,resulting in an increased transendothelial loss of fluid tothe extravascular compartment. In contrast, the second hypothesisfocuses on vascular ‘underfilling’ due to inappropriatelylow aldosterone levels. The second hypothesis is based on theassumption that a compensatory increase in the circulating fluidvolume is required in normal pregnancy to support fetal substratedelivery. According to the second concept, maternal blood pressureincreases due to counter-regulatory mechanisms when placentalblood supply is reduced [2]. In support of the ‘underfilling’hypothesis are observations that a     

Impact of early dietary gamma-linolenic acid supplementation on atopic eczema in infancy

Polyunsaturated fatty acids (PUFAs) are components of cell membranes and may play an immunomodulating role in the pathogenesis of atopic dermatitis (AD). The goal was to determine the impact of PUFAs on AD by dietary supplementation of infants. Based on the parents' decision on their babies' primary feeding, mothers and newborns were randomized to the supplementation with gamma-linolenic acid (GLA) or placebo for up to 6 months. Breastfed infants received GLA by supplementing their mothers. Formula diet was commercial whey hydrolysate unsupplemented with PUFAs. Of 131 eligible infants, 24 developed AD within the first year of life. Of these, nine belonged to the exclusively breastfed group (n = 58), 14 to the combined-fed group (n = 53), and one to the never breastfed group (n = 20). We could not find an influence of GLA on the development of AD. In subjects with AD, at 1 yr of age the serum-immunoglobulin E (IgE) was the lowest in the GLA-supplemented group A-subjects. In the GLA-supplemented group, GLA-levels in breast milk were similar in atopic and non-atopic infants. In the non-supplemented group the GLA-content of breast milk was 0.07% of total fatty acids in atopic infants vs. 0.17% in non-atopic infants (p < 0.01). Dietary GLA-supplementation could not prevent AD. Interestingly, the number of infants developing AD was the lowest in never breastfed children. In infants suffering from AD, GLA-supplementation seemed to reduce total IgE in the first year of life.     

A critical assessment of allergen component-based in vitro diagnosis in cherry allergy across Europe

BACKGROUND: Food allergy to cherry occurs throughout Europe, typically with restricted oral reactions in the central and northern parts but with frequent systemic reactions in the Mediterranean region. Previous studies have demonstrated insufficient sensitivity of commercially available cherry extract reagents in the diagnosis of cherry allergy. OBJECTIVE: To assess the diagnostic performance of specific IgE tests based on recombinant cherry allergens in comparison with an extract-based assay and to skin prick test (SPT). A secondary objective was to analyse the frequency of systemic reactions in cherry-allergic subjects across Europe, including the largest population of LTP-sensitized subjects from central Europe studied to date. METHODS: A total of 186 subjects from central Europe and Spain were studied. Serum IgE was analysed with ImmunoCAP tests carrying rPru av 1, 3 and 4, combined and separately, and cherry extract. RESULTS: Among the central European cherry allergics, the mix of rPru av 1, 3 and 4 had a sensitivity of 95%, compared with 65% for cherry extract, and the IgE binding capacity of the recombinant mix was considerably higher. The sensitivity of the two tests was more comparable in the Spanish population, 95% and 86%, respectively. The recombinant allergen ImmunoCAP equalled SPT in terms of sensitivity and specificity. Consistent with previous reports, major geographic differences in sensitization pattern and prevalence of systemic reactions were found. A significantly higher rate of systemic reactions was found in Spanish patients sensitized to Pru av 3 whereas German patients sensitized to LTP only had oral allergy syndrome. CONCLUSIONS: The recombinant cherry allergen ImmunoCAP is a highly sensitive diagnostic tool, clearly superior to any diagnostic method based on cherry extract. Three cherry allergens are sufficient for detecting sensitization in 95% of cherry-allergic subjects. Systemic reactions are common in LTP-sensitized individuals but seem to require at least one additional causative factor.     

Lymphocytic and collagenous colitis: the emerging entity of microscopic colitis. An update on pathophysiology, diagnosis and management.

Microscopic colitis (MC) encompasses the two morphologically distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). MC was first described less than 30 years ago but is presently recognized as a relatively common cause of chronic diarrhea in the adult population. Remarkably, up to 10% of adults who have a colonoscopy for the investigation of chronic diarrhea, and have endoscopically normal appearing mucosa, may have MC. Patients with MC generally present with chronic diarrhea, which can be associated with cramping and bloating. Endoscopic and radiological examinations are usually normal. Histological assessment reveals inflammation consisting predominantly of lymphocytic infiltration, and a thickened subepithelial collagen band is diagnostic of CC. Both LC and CC can be associated with autoimmune diseases such as celiac disease, diabetes, arthritis and thyroiditis, yet the mechanisms involved in the pathogenesis remain unclear. Emerging studies suggest that a stepwise approach be taken in the medical management of MC. This approach includes antidiarrheal agents and stopping of any offending agents; budesonide or bismuth subsalicylate; and cholestyramine or 5-acetylsalicylic acid agents. In resistant cases, oral corticosteroids and other immune modulatory therapy have been used.