Aware and unaware perception in hemispatial neglect: evidence from a stem completion priming task

The current study used the process dissociation procedure in conjunction with a stem-completion priming task to disentangle the influences of aware and unaware perception in patients with hemispatial neglect. One lateralized picture prime was presented simultaneously with a filler picture followed by a centrally presented word stem. In the inclusion condition participants were asked to complete the word stem with the previously presented picture name; in the exclusion task they were asked to complete the stem with the name of a picture other than the one previously presented. Findings indicated that neglect patients had reduced unaware perception of pictures presented in the left visual field and an absence of awareness for those same pictures. In addition, patients had reduced awareness for right visual field pictures, but unaware perception remained intact. These findings suggest that observations of preserved information processing in neglect are due to residual unaware perception and not due to residual awareness of information in the neglected hemispace.     

A simple technique for high-throughput screening of drugs that modulate normal and psoriasis-like differentiation in cultured human keratinocytes

Established treatments for psoriasis act ei-ther on hyperproliferation, inflammation, aberrant epidermal differentiation or a combination of these aspects of the disease. Potential new drugs for treatment of psoriasis or other disorders with abnormalities in epidermal differentiation can be identified by high-throughput screening of large compound libraries using surrogate markers for the disease. Here we describe a screening model to detect pharmacologically active drugs in two keratinocyte-based, 96-well culture models that use expression of cytokeratin 10 (CK10) and skin-derived antileucoprotease (SKALP)/elafin as markers for normal and psoriatic differentiation, respectively, and allow multiple parameters to be determined from a single well. In this model we tested a number of compounds in a pharmacological range from 10(-7) to 10(-5) M, including known antipsoriatic drugs, and experimental drugs that are potentially useful in the treatment of psoriasis. All-trans-retinoic acid, dithranol and the p38 mitogen-activated protein (MAP) kinase inhibitor SB220025 displayed a strong inhibitory effect on SKALP expression while cyclosporin A, dexamethasone, the vitamin D(3) derivative calcipotriol and the p38 MAP kinase inhibitor SB203580 showed only moderate inhibition. Methotrexate and dimethylfumarate did not affect the expression of SKALP. With respect to CK10 expression, all-trans-retinoic acid, calcipotriol, SB203580 and SB220025 exhibited strong inhibition while dithranol showed only moderate suppression of this normal differentiation marker. Expression levels of CK10 were not significantly affected by dexamethasone, methotrexate, cyclosporin A or dimethylfumarate. This model system parallels most, but not all, findings on the in vitro effect of known antipsoriatic drugs on keratinocytes. In addition, the model identifies p38 MAP kinase inhibitors as potent suppressors of differentiation-associated gene expression. Although further delineation and validation of this model is required, we conclude that the system is amenable to down-scaling and application as a high-throughput screen for differentiation-modifying compounds.     

Phenobarbital-induced drug metabolism in man

Phenobarbital and antipyrine half-lives were measured in 31 subjects. A high correlation (r = 0.87) was found for the plasma elimination rates of the two drugs, suggesting the same or a similar route or a common regulatory control of their metabolism. The half-lives of phenobarbital and antipyrine also correlated highly with the aryl hydrocarbon hydroxylase (AHH) inducibilities in mitogen-stimulated lymphocytes of the same individuals. In the second part of the study, plasma antipyrine half-lives were measured in 22 subjects after a single oral dose of 18 mg/kg, and the AHH inducibilities were determined in their cultured lymphocytes. After 7 days on phenobarbital at aryl hydrocarbon hydroxylase inducibilityadjusted doses ranging between 1.0 and 2.0 mg/kg daily, the antipyrine half-lives were measured again and the percentage of decrease between the initial and second antipyrine half-lives was determined. Shortening of the plasma half-lives occurred in all subjects to various degrees, ranging between 13.3 and 30.6%. However, under our experimental conditions in which the dose of phenobarbital was adjusted to the individual rates of metabolism of the inducing agent, no relationship could be found between the initial antipyrine half-life and the percentage of shortening of its plasma half-life, such as had been reported by several authors.     

Long Term Follow-up of HNPCC Gene Mutation Carriers: Compliance with Screening and Satisfaction with Counseling and Screening Procedures

Hereditary non polyposis colorectal cancer (HNPCC) is a hereditary predisposition to colorectal and endometrial cancer, caused by mutations of the mismatch repair (MMR) genes MSH2, MLH1 and MSH6. Regular colonoscopy reduces the incidence of colorectal cancer in mutation carriers dramatically. The aim of this study was to evaluate the use of colonoscopy by proven HNPCC mutation carriers. We also evaluated the satisfaction with the counseling and screening procedures at the long term. A questionnaire survey was performed among 94 proven MMR gene mutation carriers. Data were analyzed using univariate and multivariate analysis. The average time of follow-up was 3,5 years (range 0.5–8.5 years). The response rate was 74%. The proportion of unaffected mutation carriers under colonoscopic screening increased from 31 to 88% upon genetic testing, and for gynecological screening from 17 to 69%. However, more than half of the responders experienced colonoscopy as unpleasant or painful. About 97% felt well informed during counseling, and 88% felt sufficiently supported. Ten percent of the responders reported a high cancer worry that was significantly (P = 0.007) associated with a high perceived cancer risk. Six responders (9%) regretted being tested. Remarkably, of 4 of these 6 a close relative died recently of cancer. Problems with obtaining a disability or life insurance or mortgage were experienced by 4 out 10 healthy carriers opting for these services. In conclusion, genetic testing for HNPCC considerably improves compliance for screening, which will result in a reduction of HNPCC-related cancer morbidity and mortality in mutation carriers. Most HNPCC gene mutation carriers cope well with their cancer susceptibility on the long term.     

Comorbidity of chronic diseases

Although much research has been done on the impact of chronic illness on quality of life, still relatively little is known about the role of comorbidity. Given the growing number of (older) people with multiple chronic conditions, more information is needed on the effects of specific disease combinations for preventive purposes. In a nationwide representative sample of 1673 non-institutionalized chronic disease patients (recruited in 56 general practices) in The Netherlands, we assessed the separate and joint effects of cardiovascular disease, cancer, arthritis, chronic respiratory disease, diabetes mellitus, and thyroid dysfunction on physical and mental functioning. Data on medical diagnoses were provided by the general practitioners; data on physical and mental functioning were collected by a patient survey (SF-36). Compared to reference data of the general population, physical functioning appeared to be worse in all six diagnostic groups, whereas mental functioning was more or less comparable. Patients with arthritis or those suffering from comorbidity reported the lowest levels of physical functioning. Synergistic effects of combinations of diabetes, cardiovascular disease and/or chronic respiratory disease were found, indicating that patients suffering from these disease combinations run a higher risk of physical disability than could be expected from their separate effects.     

The Dutch Heart Health community intervention 'Hartslag Limburg': results of an effect study at individual level

'Hartslag Limburg' (Dutch for Heartbeat Limburg), a regional cardiovascular diseases (CVD) prevention program, integrates a community strategy and a high-risk strategy to reduce CVD risk behaviors. The present paper focuses on the effects of the community intervention on fat intake and physical activity. The project was based on community organization principles and health education theories and methods. In order to implement the intervention, nine local Health Committees were set up, each organizing activities that facilitate and encourage people to adopt a healthier lifestyle. A pre-test-post-test control group design with two post-tests was used to evaluate the intervention. At baseline, representative random cohort research samples were selected in the Maastricht region and in a control region. Data on fat intake and physical activity, and on the psychosocial determinants of these behaviors, were gathered by means of mail surveys. The present study indicates that the intervention had a significant effect on fat reduction, especially among respondents aged 相似文献   

Eosinophilia in the ethmoid mucosa and its relationship to the severity of inflammation in chronic rhinosinusitis

BACKGROUND: The aim of this study was to analyze histopathologically mucosal inflammation in patients with chronic rhinosinusitis. In addition, we assessed tissue eosinophilia in relation to the severity of inflammation and to the computer tomographic (CT) findings. METHODS: Forty-eight pathological sinus mucosa specimens obtained during functional endoscopic sinus surgery were stained by hematoxvlin and eosin. Total inflammatory cells and eosinophils were quantified. The preoperative CT scans were scored by the staging system of Lund-MacKay. RESULTS: The grade of the eosinophilic infiltration in the diseased sinus mucosa correlated significantly with the severity of the mucosal inflammation. Allergy or asthma had no effect on the proportion of the eosinophilic infiltrate. The CT scan scores assessed by the Lund-MacKay system correlated significantly with the severity of the inflammatory cellular infiltrate. The correlation between the CT scan scores and the eosinophilic infiltrate of the mucosa was close to significant. CONCLUSION: Eosinophilic mucosal inflammation represents the most severe inflammatory changes of the mucosa. Twenty to forty percent of the patients with chronic rhinosinusitis had no eosinophilic inflammation of the mucosa. The CT-staging system of Lund-Mackay correlated with the extent of mucosal inflammation.     

Nasalance,nasality, voice,and articulation after uvulopalatopharyngoplasty

OBJECTIVES/HYPOTHESIS: The main purpose of the study was to determine the impact of uvulopalatopharyngoplasty (UPPP) on nasalance and nasality. It was hypothesized that nasalance would change from the presurgical to the postsurgical condition because the surgical protocol involves removal of palatal tissue. An additional objective of the study was to provide objective and subjective data about changes in voice and articulation after UPPP. Because the surgical procedure of UPPP does not involve laryngeal tissue, it was hypothesized that the voice characteristics remain relatively stable. Because of removal of effective velar length, articulation problems of the uvular /R/ can occur in the Dutch language. STUDY DESIGN: Prospective study in which 26 men were studied before (1 week before UPPP) and after (3 weeks after UPPP) surgery. METHODS: The Nasometer was used to obtain nasalance scores. The mirror-fogging test, a perceptual evaluation of each subject's readings, and the Gutzmann and the Bzoch hypernasality tests were used for the assessment of nasality. For the assessment of articulation, a phonetic analysis was performed. Voice assessment included a perceptual rating of the voice and a determination of fundamental frequency. RESULTS: No significant differences were found between the conditions before and after surgery regarding nasalance (except for the vowel /i/), nasality, and voice. Regarding articulation, only 1 patient showed a derhotacized /R/. CONCLUSIONS: The findings of the study indicate that UPPP does not have an impact on nasality, voice, and articulation. Regarding nasalance, no significant nasalance change occurred after UPPP, except for the high vowel /i/.