[A cecum carcinoma and liver and peritoneal lesions]. / Een caecumtumor én lever- en peritoneumafwijkingen.

A 37-year-old male presented with acute lower right abdominal pain. A CT-scan showed a cecal mass. During laparoscopic right colectomy, multiple liver lesions and peritoneal deposits were seen. Histology confirmed pT4aN0 cecum carcinoma, but the liver lesions were consistent with sarcoidosis, and the peritoneal deposits were suggestive of benign mesothelioma.

The low anterior resection syndrome in a reference population: prevalence and predictive factors in the Netherlands.

AIM: The low anterior resection syndrome (LARS) severely affects quality of life (QoL) after colorectal cancer surgery. There are no data about these complaints and the association with QoL in a reference population. The aim of this study was to assess LARS and the association with QoL in a reference population. METHODS: Six hundred patients who visited the outpatient clinic because of general or trauma surgical indications were asked to participate in this study. They received an invitation letter containing three validated questionnaires to assess LARS (assessed with the LARS score) and both general [European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30] and colorectal-specific (EORTC QLQ-CR29) QoL. RESULTS: Five hundred and one respondents could be included for the analyses. The median age at inclusion was 68 years and 47.3% were men. Major LARS was observed in 15% of patients (11.4% in men and 18.9% in women, P = 0.021). Women reported more urgency (P = 0.070) and incontinence for both flatus (P < 0.001) and stool (P = 0.063) compared to men. In univariate analyses, women reported major LARS significantly more often than men (OR 1.82; 95% CI 1.10-3.01). Patients with major LARS scored significantly worse in most QoL domains compared to patients with no/minor LARS. CONCLUSION: This is the first study demonstrating major LARS and the association with QoL in a reference population of patients without colorectal cancer. Our data can assist in the interpretation of LARS in past and future research about abdominal complaints after colorectal cancer surgery.

Apraxia of speech and cerebellar mutism syndrome: a case report.

BACKGROUND: Cerebellar mutism syndrome (CMS) or posterior fossa syndrome (PFS) consists of a constellation of neuropsychiatric, neuropsychological and neurogenic speech and language deficits. It is most commonly observed in children after posterior fossa tumor surgery. The most prominent feature of CMS is mutism, which generally starts after a few days after the operation, has a limited duration and is typically followed by motor speech deficits. However, the core speech disorder subserving CMS is still unclear. CASE PRESENTATION: This study investigates the speech and language symptoms following posterior fossa medulloblastoma surgery in a 12-year-old right-handed boy. An extensive battery of formal speech (DIAS = Diagnostic Instrument Apraxia of Speech) and language tests were administered during a follow-up of 6 weeks after surgery. Although the neurological and neuropsychological (affective, cognitive) symptoms of this patient are consistent with Schmahmann's syndrome, the speech and language symptoms were markedly different from what is typically described in the literature. In-depth analyses of speech production revealed features consistent with a diagnosis of apraxia of speech (AoS) while ataxic dysarthria was completely absent. In addition, language assessments showed genuine aphasic deficits as reflected by distorted language production and perception, wordfinding difficulties, grammatical disturbances and verbal fluency deficits. CONCLUSION: To the best of our knowledge this case might be the first example that clearly demonstrates that a higher level motor planning disorder (apraxia) may be the origin of disrupted speech in CMS. In addition, identification of non-motor linguistic disturbances during follow-up add to the view that the cerebellum not only plays a crucial role in the planning and execution of speech but also in linguistic processing. Whether the cerebellum has a direct or indirect role in motor speech planning needs to be further investigated.

A screening algorithm for diagnosing bacterial gastroenteritis by real-time PCR in combination with guided culture.

We have introduced a real-time PCR for the simultaneous detection of Campylobacter jejuni, Salmonella spp., Shigella spp./enteroinvasive Escherichia coli and Yersinia enterocolitica in fecal samples in our routine laboratory. This new approach showed consistent results, with minimal inter-sample variation. When compared to conventional culture, the hands-on time decreased by 13 h/wk, and the median turnaround time drastically shortened from 73 to 29 h (P < .0001). Moreover, the detection rate of the targeted pathogens seemed to increase: the positivity rate registered over a twelve month period increased from 4.98% when using bacterial culture, compared to 8.56% when using real-time PCR (P < .0001). For antimicrobial susceptibility testing, samples that are found to be PCR positive are additionally cultured after the PCR result is known. Using this algorithm, we got a positive culture for 71.0% of the PCR positive samples. The samples missed by guided culture had significantly higher quantification cycle (Cq) values compared to the samples picked up by guided culture (P = .0003). Finally; we also tested the effect of extended sample storage on the performance of guided culture. Storage time prior to inoculation did have an effect on the positivity rate of culture; interestingly, these effects were clearly species-dependent.

Subcortical language and non-language mapping in awake brain surgery: the use of multimodal tests.

BACKGROUND: Awake craniotomy is currently considered the gold standard to maximise the extent of resection and to minimise postoperative deficits in patients with supratentorial tumours near eloquent areas. In addition to direct electrical stimulation (DES) of the cortex, intraoperative subcortical mapping is increasingly used as it optimises the benefit-to-risk ratio by decreasing (permanent) postoperative neurological deficits. However, only little attention has been paid to subcortical mapping procedures and especially the tasks to be used. METHODS: In this article, language and non-language testing at the subcortical level is described and discussed by means of three right-handed cases with a glioma in the left hemisphere. To assess subcortical functions, a multimodal test named the Quick Mixed Test was developed (QMT). Pre-, intra- and postoperative test results are described and discussed in detail. RESULTS: Based on the analysis of these preliminary observations, a number of clinical recommendations for intraoperative subcortical mapping may be made: (1) the selection of a set of language and non-language tests needs to be tailored according to the functional corticosubcortical regions affected by the tumoral lesion and the patient's characteristics (job/hobby/daily life activities); (2) language and non-language tests should be presented in a multimodal and alternating way during subcortical stimulation since this approach enables screening various functions simultaneously or in a very short period of time and (3) spontaneous speech is a useful adjunct to standardised tests since it most resembles daily life conversation. CONCLUSION: Administration of multimodal tests during subcortical DES such as the experimental QMT may facilitate identification of eloquent pathways leading to avoidance of permanent neurological impairments.

Evaluation of a real-time multiplex PCR for the simultaneous detection of Campylobacter jejuni, Salmonella spp., Shigella spp./EIEC, and Yersinia enterocolitica in fecal samples.

Conventional diagnosis of infectious diarrhea caused by bacteria is time-consuming, labor-intensive, and has a suboptimal sensitivity. We have therefore developed a multiplex real-time polymerase chain reaction (PCR) for the simultaneous detection of Campylobacter jejuni, Salmonella spp., Shigella spp./enteroinvasive Escherichia coli (EIEC), and Yersinia enterocolitica in fecal samples. No cross reactivity between the different pathogens was observed, and the multiplex setup of the assay did not have an impact on the sensitivity of the PCR. The analytical sensitivity was 87 CFU/mL for C. jejuni, 61 CFU/mL for Shigella spp./EIEC, 5,528 CFU/mL for Salmonella spp., and 1,306 CFU/mL for Y. enterocolitica. An extensive validation of the assay was performed by testing 1,687 patient samples by both PCR and with conventional techniques. The use of PCR increased the overall clinical sensitivity from 78 to 100 % (p < 0.0001), the specificity was 99.4 % for the PCR, compared with 99.9 % for conventional culture. The novel PCR assay allows for rapid, sensitive, inexpensive, and high-throughput testing of the most common bacterial causes of gastroenteritis.

The Dutch Linguistic Intraoperative Protocol: a valid linguistic approach to awake brain surgery.

Intraoperative direct electrical stimulation (DES) is increasingly used in patients operated on for tumours in eloquent areas. Although a positive impact of DES on postoperative linguistic outcome is generally advocated, information about the neurolinguistic methods applied in awake surgery is scarce. We developed for the first time a standardised Dutch linguistic test battery (measuring phonology, semantics, syntax) to reliably identify the critical language zones in detail. A normative study was carried out in a control group of 250 native Dutch-speaking healthy adults. In addition, the clinical application of the Dutch Linguistic Intraoperative Protocol (DuLIP) was demonstrated by means of anatomo-functional models and five case studies. A set of DuLIP tests was selected for each patient depending on the tumour location and degree of linguistic impairment. DuLIP is a valid test battery for pre-, intraoperative and postoperative language testing and facilitates intraoperative mapping of eloquent language regions that are variably located.

Validation of a new panel of automated chemiluminescence assays for von Willebrand factor antigen and activity in the screening for von Willebrand disease.

INTRODUCTION: The diagnosis of von Willebrand disease (VWD) largely depends on the results of von Willebrand factor (VWF) antigen and activity. Recently, a new automated VWF:RCo assay on Acustar was developed. This assay panel for VWD also contains a new antigen (VWF:Ag) test. In this study, both chemiluminescence tests (HemosIL VWF:Ag and VWF:RCo) were evaluated. MATERIALS AND METHODS: Imprecision, limit of detection (LOD), and linearity were evaluated. Method comparison (with VWF:Ag latex assay and VWF:RCo by aggregometry) was performed and diagnostic performance of the new test panel was examined. RESULTS: The imprecision was 7%, and the LOD was 0.2 IU/dL for both assays. Dilution series showed a large linearity for both HemosIL VWF:Ag (0-300 IU/dL) and VWF:RCo (0-200 IU/dL) and method comparison studies revealed good agreement with the currently used VWD panel. The new panel showed adequate diagnostic performance: diagnostic sensitivity was 100% and diagnostic specificity 82% compared with the VWF:Ag latex assay and VWF:RCo by aggregometry. In addition, the new HemosIL Acustar VWF:Ag and HemosIL Acustar VWF:RCo are more sensitive for VWD than the currently used assays. CONCLUSIONS: This new VWD test panel has adequate laboratory characteristics and allows fully automated and simultaneous analysis of the VWF:Ag and VWF:RCo.

Evaluation of the ESPLINE® Influenza A & B-N assay for the detection of influenza A and B in nasopharyngeal aspirates.

Several direct antigen tests for the detection of influenza often lack sensitivity compared to immunofluorescence (IF) on the specimens and viral culture (VC). We evaluated the performance of a rapid test, the ESPLINE® Influenza A & B-N assay. A total of 302 respiratory specimens were collected at the University Hospital of Antwerp. A first group of 60 samples taken during the H1N1 outbreak (2009-2010) and a second group of 242 samples stored during the seasonal influenza epidemics (2000-2009) were analyzed with the ESPLINE® test. A subset of samples were also evaluated with the BinaxNOW Influenza and the Clearview Exact Influenza. The results were compared to IF on the specimens, VC with IF, and the combination of both, which was considered as the gold standard. The ESPLINE® test's overall sensitivity and specificity were 91% and 97%, during the H1N1 season 80% and 93%, and for the detection of seasonal influenza 93% and 97%, respectively. In comparison to the BinaxNOW Influenza and the Clearview Exact Influenza, all tests demonstrated a similar specificity of 92.0-100% but a significantly different sensitivity of 44.4-86.0%, with the ESPLINE® test being significantly more sensitive. Due to its very good performance and simplicity, the ESPLINE® test facilitates urgent testing. The test seems less sensitive to detect H1N1 compared to seasonal influenza, although the difference is borderline not significant (p = 0.067).

Is there an interaction between interleukin-10 and interleukin-22?

Interleukin(IL)-10 and IL-22 are structurally related cytokines. Their heterodimeric receptors consist of the cytokine-specific chains IL-10R1 and IL-22R1, respectively, and the common chain IL-10R2. This study focused on the question of whether IL-10 modulates IL-22 effects and vice versa. This question is important because IL-10 and IL-22 exert anti- and proinflammatory effects, respectively, and, as we show here, are simultaneously present in both systemic and local inflammation. The revealed lacking concomitance of IL-10R1 and IL-22R1 on identical cells excluded any possible interaction between IL-10 and IL-22 apart from the competition for IL-10R2. To study this competition, monocytes and hepatocytes were chosen. The dependence of the cytokine action on IL-10R2 was verified. Interestingly, no influence of IL-22 on IL-10 effects was observed. The same was true when IL-22 was used in complex with IL-22-binding protein. Similarly, no influence of IL-10 was found on IL-22 action. This missing competition seemed to be due to a lack of binding between IL-10R2 and the native cytokines in the absence of their corresponding R1 chain. However, IL-10R2 interacted with defined IL-10- and IL-22-derived peptides supporting the hypothesis that cytokine binding to its corresponding R1 chain creates a binding site on this cytokine for IL-10R2.

Tenascin expression in relation to stromal tumour cells in canine gastrointestinal epithelial tumours.

The expression of tenascin, alpha-smooth muscle actin (alpha-SMA), desmin and vimentin was investigated immunohistochemically in the stroma of normal canine stomach, small intestine and colon, and in 30 epithelial tumours of the canine stomach, small intestine or colon. In addition, "co-localization" of tenascin and alpha-SMA was investigated by double immunohistochemistry. Tenascin was absent in the normal gastric mucosa but present in the normal intestine, with a gradual increase in immunolabelling intensity from the cryptal glands to the surface epithelium. Tenascin expression was greater in all adenomas and carcinomas than in normal tissues. Two different patterns of tenascin expression were observed in all carcinomas, irrespective of their site. In well-differentiated tumour regions of both gastric and intestinal tumours, a fibrillary sub-glandular expression was observed; in poorly differentiated tumour regions, however, the expression pattern was diffuse. Incomplete invasion of the muscularis mucosae was accompanied by thickening and increased tenascin expression. In normal stomach and intestines, alpha-SMA and desmin were demonstrated in pericryptal myofibroblasts and smooth muscle cells of the muscle layers. In colonic adenomas and gastric and intestinal carcinomas, alpha-SMA was demonstrated in all stromal cells surrounding tumour cells. In contrast to alpha-SMA labelling, desmin labelling was negative in tumour stromal cells (in both gastric and intestinal tumours), except in tumour regions close to the muscularis mucosae. This suggested that myofibroblasts in gastric and intestinal tumours originated from pre-existing fibroblasts, except in tumour regions close to the muscularis mucosae, where the myofibroblasts seemed to originate from smooth muscle cells of the muscularis mucosae. There was a strong co-localization of tenascin and alpha-SMA-expressing myofibroblasts, suggesting that myofibroblasts are responsible for tenascin secretion.

Neurophysiologic predictors of treatment response to fluoxetine in major depression.

Treatment with antidepressants is marked by heterogeneity of response; predicting individual response to any given agent remains problematic. Neuroimaging studies suggest that response is accompanied by physiologic changes in cerebral energy utilization, but have not provided useful markers at pretreatment baseline. Using quantitative EEG (QEEG) techniques, we investigated pretreatment neurophysiologic features to identify responders and non-responders to fluoxetine. In a double-masked study, 24 adult subjects with current major depression of the unipolar type were studied over 8 weeks while receiving fluoxetine (20 mg QD) or placebo. Neurophysiology was assessed with QEEG cordance, a measure reflecting cerebral energy utilization. Response was determined with rating scales and clinical interview. Subjects were divided into discordant and concordant groups based upon the number of electrodes exhibiting discordance. The concordant group had a more robust response than the discordant group, judged by lower final Hamilton Depression (HAM-D) mean score (8.0+/-7.5 vs. 19.6+/-4.7, P = 0.01) and final Beck Depression Inventory (BDI) mean score (14.0+/-9.4 vs. 27.8+/-3.7, P = 0.015), and by faster reduction in symptoms (HAM-D: 14.0+/-5.0 vs. 23.8+/-4.1, P = 0.004 at 1 week). Groups did not differ on pretreatment clinical or historical features. Response to placebo was not predicted by this physiologic measure. We conclude that cordance distinguishes depressed adults who will respond to treatment with fluoxetine from those who will not. This measure detects a propensity to respond to fluoxetine and may indicate a more general responsiveness to antidepressants.

Autoreactive human T cell lines recognizing ribosomal protein L7.

Sera of patients suffering from systemic lupus erythematosus (SLE) frequently contain oligoclonal IgG autoantibodies with high affinity for the ribosomal protein L7 (rpL7). The humoral autoimmune response to rpL7 apparently is driven by antigen and T cell dependent. In order to analyze the T cell response to rpL7 we cultured peripheral blood lymphocytes of healthy individuals and SLE patients in the presence of recombinant rpL7. After 10 days, the cytokine response to re-stimulation with rpL7 was examined using a spot-ELISA. Measuring IFN-gamma secretion, the T cells of two patients and four healthy donors showed a significant increase in the number of spots as compared to control cells. Secretion of IL-4 or IL-10 was not detected. From the antigen-stimulated primary cultures we established by limiting dilution cloning six rpL7-reactive, IFN-gamma-secreting T cell lines which show a CD3+CD4+CD8- phenotype. One line additionally was shown to be positive for HLA-DR and CD45R0, but negative for CD27 and CD31. The cell lines carry alphabeta TCR chains which differ from each other in sequence and specificity. rpL7 fragments rich in basic amino acids could be identified as epitopes recognized by the TCR of three cell lines. Recognition of rpL7 is HLA-DR6 restricted or respectively HLA-DP restricted in the two cell lines analyzed.

Alteration of brain noradrenergic activity in rhesus monkeys affects the alerting component of covert orienting.

Experiments were conducted to elucidate the role of the noradrenergic neurotransmitter system in arousal and the orienting of attention. Rhesus monkeys were trained to perform a peripherally cued, covert orienting task for juice reward, and their manual reaction times (RTs) to visual stimuli were measured. The effects of parenteral injections of the alpha-2 adrenergic agonists clonidine and guanfacine, and normal saline were compared on the covert task. We assessed 1) overall error rates, 2) the difference in RTs between validly and invalidly cued trials (validity effect), 3) the difference in RTs between neutral and no-cue trials (alerting effect), 4) target location (visual field), and 5) cue-target interval. Changes in noradrenaline levels produced by clonidine (and to a lesser extent guanfacine) significantly decreased the alerting effect, and lowered RTs to stimuli in the left visual field, but did not change the validity effect, suggesting that noradrenaline is involved in maintaining non-spatial, sensory readiness to external cues but not in the shifting of the attentional focus.

Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance.

Experiments were conducted to elucidate the role of the cholinergic neurotransmitter system in arousal and the orienting of attention to peripheral targets. Rhesus monkeys and humans fixated a visual stimulus and responded to the onset of visual targets presented randomly in two visual field locations. The target was preceded by a valid cue (cue and target at the same location), an invalid cue (cue and target to opposite locations), a double cue (cues to both spatial locations, target to one), or, the cue was omitted (no-cue, target to either location). Reaction times (RTs) to the onset of the target were recorded. For monkeys, systemic injections of nicotine (0.003-0.012 mg/kg) or atropine (0.001-0.01 mg/kg), but not saline control injections, reduced mean RTs for all trials, indicating general behavioral stimulation. In addition, nicotine significantly reduced RTs for invalid trials but had little additional effect on those for valid, double, or no-cue trials. Virtually identical effects were observed for human chronic tobacco smokers in performing the same task following cigarette smoking. Injections of atropine in monkeys had no effect on RTs for valid or invalid trials but significantly slowed RTs in double-cue trials that did not require the orienting of attention. These results suggest that in both species, the nicotinic cholinergic system may play a role in automatic sensory orienting. In addition, the muscarinic system may play a role in alerting to visual stimuli in monkeys.