Altered cortical-amygdala coupling in social anxiety disorder during the anticipation of giving a public speech.

BACKGROUND: Severe stress in social situations is a core symptom of social anxiety disorder (SAD). Connectivity between the amygdala and cortical regions is thought to be important for emotion regulation, a function that is compromised in SAD. However, it has never been tested if and how this connectivity pattern changes under conditions of stress-inducing social evaluative threat. Here we investigate changes in cortical-amygdala coupling in SAD during the anticipation of giving a public speech. METHOD: Twenty individuals with SAD and age-, gender- and education-matched controls (n = 20) participated in this study. During the functional magnetic resonance imaging (fMRI) session, participants underwent three 'resting-state' fMRI scans: one before, one during, and one after the anticipation of giving a public speech. Functional connectivity between cortical emotion regulation regions and the amygdala was investigated. RESULTS: Compared to controls, SAD participants showed reduced functional integration between cortical emotion regulation regions and the amygdala during the public speech anticipation. Moreover, in SAD participants cortical-amygdala connectivity changes correlated with social anxiety symptom severity. CONCLUSIONS: The distinctive pattern of cortical-amygdala connectivity suggests less effective cortical-subcortical communication during social stress-provoking situations in SAD.

Evaluation of a multifaceted medication review in older patients in the outpatient setting: a before-and-after study.

BACKGROUND: The prevalence of medication-related emergency department visits and acute hospital admissions in older patients is rising due to the ageing of the population and increasing prevalence of multimorbidity and associated polypharmacy. AIM: To explore whether a combined medication review performed in the outpatient setting reduces the number of medication-related emergency department visits and hospital (re)admissions. METHOD: All consecutive patients visiting the geriatric outpatient clinic underwent a multifaceted medication review (i.e. evaluation by at least a geriatrician, and/or pharmacist and use of clinical decision support system). Subsequently, we analysed the number of, and reason for, emergency department visits, acute hospital admissions and readmissions in the year prior to and the year following the index-date (date of first presentation and medication review). RESULTS: A multifaceted medication review reduced the number of potentially medication-related emergency department visits (38.9% vs. 19.6%, p < 0.01), although the total number of ED visits or acute hospital admissions per patient in the year before and after medication review did not differ. CONCLUSION: A multifaceted medication review performed in the outpatient clinic reduced the number of potentially medication-related emergency department visits and could therefore reduce negative health outcomes and healthcare costs.

Mapping social reward and punishment processing in the human brain: A voxel-based meta-analysis of neuroimaging findings using the social incentive delay task.

Social rewards or punishments motivate human learning and behaviour, and alterations in the brain circuits involved in the processing of these stimuli have been linked with several neuropsychiatric disorders. However, questions still remain about the exact neural substrates implicated in social reward and punishment processing. Here, we conducted four Anisotropic Effect Size Signed Differential Mapping voxel-based meta-analyses of fMRI studies investigating the neural correlates of the anticipation and receipt of social rewards and punishments using the Social Incentive Delay task. We found that the anticipation of both social rewards and social punishment avoidance recruits a wide network of areas including the basal ganglia, the midbrain, the dorsal anterior cingulate cortex, the supplementary motor area, the anterior insula, the occipital gyrus and other frontal, temporal, parietal and cerebellar regions not captured in previous coordinate-based meta-analysis. We identified decreases in the BOLD signal during the anticipation of both social reward and punishment avoidance in regions of the default-mode network that were missed in individual studies likely due to a lack of power. Receipt of social rewards engaged a robust network of brain regions including the ventromedial frontal and orbitofrontal cortices, the anterior cingulate cortex, the amygdala, the hippocampus, the occipital cortex and the brainstem, but not the basal ganglia. Receipt of social punishments increased the BOLD signal in the orbitofrontal cortex, superior and inferior frontal gyri, lateral occipital cortex and the insula. In contrast to the receipt of social rewards, we also observed a decrease in the BOLD signal in the basal ganglia in response to the receipt of social punishments. Our results provide a better understanding of the brain circuitry involved in the processing of social rewards and punishment. Furthermore, they can inform hypotheses regarding brain areas where disruption in activity may be associated with dysfunctional social incentive processing during disease.

Medication in older patients reviewed multiple ways (MORE) study.

Background Polypharmacy in older patients can lead to potentially inappropriate prescribing. The risk of the latter calls for effective medication review to ensure proper medication usage and safety. Objective Provide insight on the similarities and differences of medication review done in multiple ways that may lead to future possibilities to optimize medication review. Setting This study was conducted in Zuyderland Medical Centre, the second largest teaching hospital in the Netherlands. Method This descriptive study compares the quantity and content of remarks identified by medication review performed by a geriatrician, outpatient pharmacist, and Clinical Decision Support System. The content of remarks is categorized in seven categories of possible pharmacotherapeutic problems: 'indication without medication', 'medication without indication', 'contra-indication/interaction/side-effect', 'dosage problem', 'double medication', 'incorrect medication' and 'therapeutic drug monitoring'. Main outcome measure Number and content of remarks on medication review. Results The Clinical Decision Support System (1.8 ± 0.8 vs. 0.9 ± 0.9, p < 0.001) and outpatient pharmacist (1.8 ± 0.8 vs. 0.9 ± 0.9, p = 0.045) both noted remarks in significantly more categories than the geriatricians. The Clinical Decision Support System provided more remarks on 'double medication', 'dosage problem' and 'contraindication/interaction/side effects' than the geriatrician (p < 0.050), while the geriatrician did on 'medication without indication' (p < 0.001). The Clinical Decision Support System noted significantly more remarks on 'contraindication/interaction/side effects' and 'therapeutic drug monitoring' than the outpatient pharmacist, whereas the outpatient pharmacist reported more on 'indication without medication' and 'medication without indication' than the Clinical Decision Support System (p ≤ 0.007). Conclusion Medication review performed by a geriatrician, outpatient pharmacist, and Clinical Decision Support System provides different insights and should be combined to create a more comprehensive report on medication profiles.

Depression and adipose and serum cholesteryl ester polyunsaturated fatty acids in the survivors of the seven countries study population of Crete.

BACKGROUND: Studies have shown that depression relates to biomarkers of both short- and long-term polyunsaturated fatty acid (PUFA) intake. However, it is not known which of these two biomarkers has the closest relationship to depression. OBJECTIVE: To examine the relationship of depression with both adipose tissue and serum cholesteryl ester PUFA and to assess the importance of each of these two biomarkers in relating to depression. DESIGN: Cross-sectional study of healthy elderly men from the island of Crete. SETTING: The Preventive Medicine and Nutrition Clinic, University of Crete, Greece. SUBJECTS: A total of 150 males, aged 80-96 years. The subjects were survivors of the Greek Seven Countries Study group. METHODS: Fatty acids were determined by gas chromatography in adipose tissue and serum cholesteryl esters. Information about depression was obtained through the use of the short form of the Geriatric Depression Scale (GDS-15). RESULTS: Regression analysis showed that depression related positively to age and serum cholesteryl ester arachidonic/docosahexaenoic fatty acid ratio. The only significant unadjusted correlation between depression and serum cholesteryl ester and adipose fatty acids was with adipose alpha-linolenic acid (ALA) (r = -0.31, P < 0.01). Depressed males (GDS-15 > 5) had lower adipose ALA and sum n-3 fatty acids than non-depressed ones. There were no significant differences between depressed and non-depressed males in serum cholesteryl ester fatty acids. When adipose tissue ALA was included as one of the independent measures in the regression model, the observed positive relation between GDS-15 depression and cholesteryl ester arachidonic/docosahexaenoic ratio failed to persist. Instead, there was a negative relationship between GDS-15 depression and adipose tissue ALA. CONCLUSIONS: It appears that the fatty acids of the adipose tissue are better predictors of depression than those of serum cholesteryl esters. This indicates that depression relates more strongly to long-term than to short-term fatty acid intake. The reason for this may be the reported slow rate of deposition of dietary PUFA to the brain.

Cloning and characterization of four genes of Rhizobium leguminosarum bv. trifolii involved in exopolysaccharide production and nodulation.

Four different genes of Rhizobium leguminosarum bv. trifolii strain RBL5599 involved in exopolysaccharide (EPS) production were identified by complementation of Tn5-induced EPS-deficient mutants (Exo mutants) with a cosmid bank. On one cosmid pssA was located, which was found to be almost identical to the pss4 gene from R. leguminosarum bv. viciae VF39 and highly homologous to a family of glycosyl transferases. Two pssA mutants, exo2 and exo4, were characterized and found to produce 19 and 1% of the wild-type amount of EPS, respectively. The three other genes were found to be closely linked on a different complementing cosmid. pssC revealed similarity to exoM and exoW of R. meliloti, both encoding glucosyl transferases involved in the synthesis of succinoglycan. A mutation in this gene (mutant exo50) did reduce EPS synthesis to 27% of the wild-type amount. We found an operon closely linked to pssC, consisting of two overlapping genes, pssD and pssE, that is essential for EPS production. Homology of pssD and pssE was found with cps14F and cps14G of Streptococcus pneumoniae, respectively: two genes responsible for the second step in capsule polysaccharide synthesis. Furthermore, pssD and pssE were homologous to the 5' and 3' parts, respectively, of spsK of Sphingomonas S88, which encodes a putative glycosyl transferase. Structural analysis of EPS produced by Exo mutants exo2, exo4, and exo50 showed it to be identical to that of the parental strain RBL5599, with the exception of acetyl groups esterified to one of the glucose residues being absent.

Procainamide therapy, physical performance and energy expenditure in the Schwartz-Jampel syndrome.

The effects of procainamide administration were assessed in a 5-yr-old boy with Schwartz-Jampel syndrome (chondrodystrophic myotonia). Without procainamide the resting metabolic rate was found to be significantly higher than in an age-matched control group. With a serum level of 3.8 mg l-1 procainamide a reduction of the resting metabolic rate of 22% was observed, and times needed to climb stairs and to re-open eyes after forceful contraction (blepharospasm) were significantly reduced.

Preparation and characterization of albumin-heparin microspheres.

Albumin-heparin microspheres were prepared by a two-step process which involved the preparation of a soluble albumin-heparin conjugate, followed by formation of microspheres from this conjugate or by a double cross-linking technique involving both coupling of soluble albumin and heparin and microsphere stabilization in one step. The first technique was superior since it allowed better control over the composition and the homogeneity of the microspheres. Microspheres could be prepared with a diameter of 5-35 microns. The size could be controlled by adjusting the emulsification conditions. The degree of swelling of the microspheres was sensitive to external stimuli, and increased with increasing pH and decreasing ionic strength of the medium.

Degradation and intrahepatic compatibility of albumin-heparin conjugate microspheres.

The in vitro degradation properties of glutaraldehyde cross-linked albumin and albumin-heparin conjugate microspheres (AMS and AHCMS respectively) were evaluated using light microscopy, turbidity measurements and heparin release determinations, showing that the microspheres are degraded by proteolytic enzymes such as trypsin, proteinase K and lysosomal enzymes. The degradation rate was inversely related to the cross-link density of the microspheres. After intrahepatic administration of AHCMS, cross-linked with 0.5% glutaraldehyde, to male Wag/Rij rats by injection into a mesenteric vein (intravenoportal: i.v.p.), the microspheres were entrapped in the hepatic vascular system. The AHCMS were entrapped within terminal portal veins predominantly at the periphery of the liver. The AHCMS were degraded by cellular enzymatic processes within 2 wk after injection, with a half life of approximately 1 d. Biocompatibility of AHCMS and adriamycin-loaded AHCMS was evaluated by histological assessment of the mitotic activity of liver parenchyma and inflammatory response, and by determination of liver damage marker enzymes during 4 wk after administration. Liver damage marker enzymes were not increased compared with controls, nor were adverse effects observed upon histological examination. There was no difference in response between empty and adriamycin-loaded AHCMS.

Achievement of therapeutic concentrations of cefuroxime in early preterm gestations with premature rupture of the membranes.

OBJECTIVE: To determine whether therapeutic cefuroxime concentrations can be achieved in maternal plasma, amniotic fluid (AF), neonatal plasma, placenta, and membranes in women with premature rupture of the membranes (PROM) at 27-33 weeks' gestation. METHODS: In an open nonrandomized, dose-response study, nine patients with PROM at 27-33 weeks' gestation received 1.5 g of cefuroxime intravenously three times daily. Maternal plasma and AF specimens were collected during pregnancy, and umbilical cord plasma, placenta, and membrane specimens were collected after delivery to assay cefuroxime concentrations using high-performance liquid chromatography. RESULTS: A high rate of placental transfer of cefuroxime was found. Bactericidal concentrations could be demonstrated in maternal plasma and in AF leaking from the vagina. A concentration-time curve in AF could be detected, with a peak concentration 3-4 hours after infusion. Therapeutically active levels were present in the newborns. The resorption of cefuroxime by the fetal membranes was high. CONCLUSIONS: Therapeutic concentrations of cefuroxime were found in all body fluids and tissues studied. Further study to establish the clinical utility of cefuroxime prophylaxis in PROM seems appropriate.

A gas chromatographic method for the estimation of phenprocoumon, 3-(1-phenyl-propyl)-4-hydroxycoumarin (Marcoumar, Liquamar), in human serum or plasma.

A rapid and reliable gas-chromatographic method is described for the estimation of phenprocoumon from human serum or plasma. No interference was found from other usual oral anticoagulant drugs. The method can be used for therapeutic and toxic levels. The appearance of two volatile derivatives of phenprocoumon (in constant ratio) is discussed.

Unusual structure of the exopolysaccharide of Rhizobium leguminosarum bv. viciae strain 248.

The exopolysaccharide from R. leguminosarum bv. viciae strain 248 differs from those of other Rhizobium strains with similar symbiotic behavior. 13C-N.m.r. spectroscopy of fragments generated by partial hydrolysis, together with methylation analysis and 13C-n.m.r. spectroscopy of the enzymically depolymerised exopolysaccharide, indicated the following nonasaccharide repeating-unit: [formula: see text] The locations of the acetyl and 3-hydroxybutanoyl substituents in the exopolysaccharide are assigned provisionally. R. leguminosarum bv. viciae strain 248, cured of its Sym plasmid pRL1JI, synthesised an exopolysaccharide in which the sites and degree of substitution were unchanged. A Tn5 mutant, derived from strain 248 and unable to induce nodules, synthesised small amounts of EPS that lacked galactose.

Successful recovery of a patient with thallium poisoning.

We describe a patient suffering from protracted and life-threatening thallium poisoning. She was treated with Prussian blue and forced diuresis, and made a good recovery. Cisapride may be effective in improving gastric emptying and relieving constipation resulting from the thallium and the treatment. Haematological abnormalities occurred in the early phase of the poisoning, with a prolonged fall in the CD4/8 lymphocyte ratio during recovery.

Breda virus (Toroviridae) infection and systemic antibody response in sentinel calves.

Enzyme-linked immunosorbent assays were established to detect Breda virus antigen in feces and homologous antibodies of the IgG1, IgM, and IgA isotypes in serum. With the aid of solid-phase immune-electron microscopy, torovirions in fecal material were observed. The course of natural infection was studied in 10 sentinel calves that had been obtained from different farms, and housed together at 1 week of age. They were separated from other cattle until the age of 10 months. Up to the age of 4 months, all calves regularly excreted Breda virus in the feces. Irrespective of the existence of IgG1 isotype maternal antibodies, all calves had early IgM responses in serum, but lack of IgA seroconversion. In 7 calves, antibody titer decreased below detection, whereas 3 calves had an isotype switch, resulting in persistent IgG1 titer. After introduction into the dairy herd at 10 months of age, all calves had diarrhea, and shedding of Breda virus was observed in 8 of them. Seroconversion for all antibody isotypes was observed, indicating lack of mucosal memory. In contrast, coronavirus infection in the presence of maternal antibodies led to isotype switch in all calves but one, and a memory response was observed after introduction into the dairy herd.

Association of diarrhea in cattle with torovirus infections on farms.

An epidemiologic survey was performed to determine the incidence of torovirus infections in 2 disease entities of cattle: diarrhea of replacement calves up to 2 months old, and winter dysentery of adult cattle. Samples were obtained from 187 diarrheal and 115 healthy calves from 15 farms, as well as 149 diarrheal and 67 healthy cows from 27 farms with or without winter dysentery. Enzyme-linked immunosorbent assays for detection of torovirus, rotavirus, and coronavirus antigen in feces, and of torovirus and coronavirus antibodies in serum were used to monitor infections in these groups. Torovirus was detected in 9 of the 15 farms in the study, and in 6% of calves with diarrhea, which was significantly higher than in healthy calves (2%). Seroconversion to torovirus was found significantly more often after winter dysentery episodes than on farms without a disease history; coronavirus seroconversion was less common.

The incidence of Chorioptes bovis (Acarina: Psoroptidae) on the feet of horses, sheep, and goats in the Netherlands.

The feet of horses, sheep, and goats of different breeds and from many different localities were examined for Chorioptes bovis. In horses, mites were mainly found in the Belgian and Frisian breeds (40% and 62% infected, respectively). In sheep and goats, respectively 63% and 86% were infected. In horses as well as in sheep and goats, mange-lesions were rarely seen. A number of sheep and goats were examined for mites and lesions quantitatively. In sheep all mites were restricted to the region close to the accessory digits and the claws. In goats the average number of mites was higher than in sheep, and mites could be found on all locations of the feet at least as far as the carpal and tarsal joint. Both in sheep and goats the biggest density of mites was found just below the accessory digits. When crusts were present, they were generally small and hidden under the coat. In sheep, which were housed for a long period, crusts were seen more often and were more distinct than in pastured animals. A negative correlation between the number of mites and the presence and extensiveness of crusts was observed. A possible explanation for this phenomenon is suggested. From the results of this study it is clear that there is no necessity to list chorioptic mange in sheep and goats as a notifiable disease.

Chorioptes bovis (Acarina: Psoroptidae) in some camelids from Dutch zoos.

The feet of three two-humped camels (Camelus bactrianus), one lama (Lama glama) and four alpacas (Lama pacos) from zoos and a circus in the Netherlands were examined for the mange-mite Choroptes bovis. Mites were found on two of the camels, the lama, and three of the alpacas. On one camel and one alpaca small mange lesions on the feet were present. This is the first report of Chorioptes bovis and chorioptic mange in the two-humped camel.

[Effectiveness of oxfendazole against Muellerius capillaris (Nematoda: Protostrongylidae) in goats]. / De effectiviteit van oxfendazole tegen Muellerius capillaris (Nematoda: Protostrongylidae) bij de geit.

The effectiveness of oxfendazole against the lungworm Muellerius capillaris was studied on a dairy-goat farm. The goats were treated with a single dose of 5 or 10 mg. per kg/bodyweight or with a dose of 5 mg per kg given three times at 48-hours-intervals. Within a week after treatment, the mean larval counts in the faeces were reduced by 95.7, 89.9 and 99.6 per cent respectively compared with the untreated goats. Within twelve weeks after treatment, this proportion was markedly reduced in the animals treated with a single dose of 5 or 10 mg per kg (to 41.9 and 73.0 per cent respectively), though in the group given three doses the proportion was still 95.1 per cent. Because of the marked temporary decrease of the larval counts shortly after treatment with doses which had none if any lethal effect on adult worms, it can be concluded that it is essential to continue faecal examination for several weeks or months before defining the effectiveness of an anthelmintic against M. capillaris.

An infection with the lungworm Filaroides milksi Whitlock, 1956 (Nematoda: Metastrongyloidea) in a dog from Belgium.

A one-year-old male boxer coming from Belgium was presented at the Small Animal Clinic with signs of respiratory distress which had been present for three weeks. A radiograph of the thorax showed features of peribronchitis and infiltration in both lungs. In spite of antibiotic and supportive therapy the dog died. Postmortem examination of the lungs revealed a large number of nematodes in most of the bronchioles and alveoli. These nematodes were identified as filaroides milksi, Whitlock, 1956, a lungworm of dogs which has not been reported in Europe previously.

[Dipetalonema dracunculoides (Cobbold, 1870) (Nematoda: Onchocercidae) in an imported dog]. / Dipetalonema dracunculoides (Cobbold, 1870) (Nematoda: Onchocercidae) bij een geïmporteerde hond.

Dipetalonema dracunculoides was found in the abdominal and thoracic cavities of an imported dog.