LDLR gene's promoter region hypermethylation in patients with familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein cholesterol (LDL-C) levels and a high risk of early coronary heart disease. Structural alterations in the LDLR, APOB, and PCSK9 genes were not found in 20-40% of patients diagnosed using the Dutch Lipid Clinic Network (DCLN) criteria. We hypothesized that methylation in canonical genes could explain the origin of the phenotype in these patients. This study included 62 DNA samples from patients with a clinical diagnosis of FH according to the DCLN criteria, who previously tested negative for structural alterations in the canonical genes, and 47 DNA samples from patients with normal blood lipids (control group). All DNA samples were tested for methylation in the CpG islands of the three genes. The prevalence of FH relative to each gene was determined in both groups and the respective prevalence ratios (PRs) were calculated. The methylation analysis of APOB and PCSK9 was negative in both groups, showing no relationship between methylation in these genes and the FH phenotype. As the LDLR gene has two CpG islands, we analyzed each island separately. The analysis of LDLR-island1 showed PR = 0.982 (CI 0.33-2.95; χ2 = 0.001; p = 0.973), also suggesting no relationship between methylation and the FH phenotype. Analysis of LDLR-island2 showed a PR of 4.12 (CI 1.43-11.88; χ2 = 13,921; p = 0.00019), indicating a possible association between methylation on this island and the FH phenotype.

Delayed functional maturation of human neuronal progenitor cells in vitro.

INTRODUCTION: Differentiation of neuronal progenitor cells (NPCs) in vitro into functional neurons is dependent on a complex cascade of molecular signaling pathways, many of which remain unknown. More specifically, in human NPCs the relationship between the expression of typical neuronal marker proteins and functional properties, such as firing action potential and synaptic transmission, is not well understood. In the present report, the immunocytochemical, morphological and electrophysiological changes that human NPCs undergo during neuronal differentiation in vitro were investigated. METHODS: Human NPCs were differentiated toward a neuronal phenotype. The time course of the expression of neuronal markers and morphological cell changes was mapped and passive and active electrophysiological membrane properties assessed, throughout the neuronal maturation process. RESULTS: The acquisition of neuronal markers preceded functional physiological maturation by several weeks. Cell input resistance decreased in the first 2 weeks as cells became less sensitive to input current, while cell capacitance progressively increased with continued neuronal process growth. Functional maturation was observed only by the fifth/sixth week, preceded by a marked increase in Na+ and K+ currents. In contrast, electrophysiological maturation of rodent precursor cells was observed at the end of the first week in vitro. Functionally, human neuronal cells became capable of firing action potentials and forming active synaptic contacts. Many features of the firing pattern however remained immature. CONCLUSIONS: The results showed that human NPCs develop remarkably slowly and retain immature neuronal features for a prolonged period. The importance of Na-dependent activity for proper neuronal maturation is emphasized.

Understanding the role parents play in tennis success: a national survey of junior tennis coaches.

OBJECTIVES: To assess coaches' perceptions about the role of parents and their positive and negative behaviours in junior tennis. METHODS: A national survey of 132 United States junior tennis coaches was completed. The extent and seriousness/impact of parent-child interaction problems and positive behaviours were rated. RESULTS: Parents were perceived as very important for junior tennis success. Most parents (59%) that these coaches had worked with were seen as having a positive influence on their player's development. However, the respondents also felt that 36% of parents negatively influenced their child's development. Positive parental behaviours included providing logistical, financial, and social-emotional support, as well as tennis opportunities and unconditional love. Negative parent behaviours included overemphasising winning, holding unrealistic expectations, and criticising their child. CONCLUSIONS: Findings are discussed relative to current sport parenting and athletic talent development research and theorising. The need to educate parents is emphasised.

Early predictors of mortality and morbidity after severe closed head injury.

Mortality and morbidity of 158 patients with severe head injury were studied in relation to age, and early (24-h) clinical and computed tomography data. For comparison of outcome data in survivors, a group of 32 patients with traumatic injuries to parts of the body other than the head was used as controls. Within the head-injured group, the mortality rate was 51%. Logistic regression analyses combined 13 out of 16 predictors into a model with an accuracy of 93%, a sensitivity of 90%, and a specificity of 95%. These include age, Glasgow Coma Scale (GCS) score, pupillary reactivity, blood pressure, intracranial pressure, blood glucose, platelet count, body temperature, cerebral lactate, and subdural, intracranial, subarachnoid, and ventricular hemorrhage. At 6 months postinjury, head-injury survivors and trauma controls were evaluated with the Glasgow Outcome Scale (GOS), a neuropsychological test battery and the Sickness Impact Profile (SIP). Head-injury survivors had a higher proportion of disabilities and neuropsychological dysfunctions than trauma controls. They also report more quality of life-related functional limitations on the SIP scales for mobility, intellectual behavior, communication, home management, eating, and work. Linear regression analysis resulted in age being the only important predictor of outcome on the GOS, the GCS score being the best predictor of neuropsychological functioning, and pupillary reactivity being the most predictive for self-reported quality of life as measured by SIP. Those factors important for predicting mortality (clinical variables such as ICP or blood glucose level, and CT observations) failed to show any significant relationship with morbidity.

Cerebral perfusion pressure and intracranial pressure in relation to neuropsychological outcome.

OBJECTIVE: The study attempted to examine the relationship between neuropsychological functioning and reduced cerebral perfusion pressure (CPP), raised intracranial pressure (ICP), and reduced mean arterial pressure (MAP), monitored during intensive care treatment. DESIGN: This prospective follow-up study included consecutive patients and evaluated outcome at 6 months postinjury by the administration of a neuropsychological test battery. SETTING: The study was conducted at the University Hospital of Gent, Belgium. PATIENTS AND PARTICIPANTS: Over a 30-month period, 43 patients were included. Inclusion criteria were the following: hospital admission following closed head injury. ICP monitoring, no medical history of central nervous system disease or mental retardation, survival for at least 6 months, and informed consent for participation. INTERVENTIONS: All patients received the hospital's standard treatment for head injury, which remained unchanged during the study period. MEASUREMENTS AND RESULTS: Reduced CPP was analyzed using the number of observed values below 70 mmhg, raised ICP using the number of values above 20 mmHg, and MAP using the number of values below 80 mmHg. The neuropsychological test battery included 11 measures of attention, information processing, motor reaction time, memory, learning, visuoconstruction, verbal fluency, and mental flexibility. No linear relationships were found between overall neuropsychological impairment and episodes of reduced CPP, raised ICP, or reduced MAP. CONCLUSIONS: Although reduced CPP and raised ICP are frequent, often fatal, complications of head injury, in survivors they do not seem to be related to later neuropsychological functioning.

Subjective complaints versus neuropsychological test performance after cardiopulmonary bypass.

The study by Newman et al. (Journal of Psychosomatic Research, 1989) compared subjective reports of cognition with assessed cognitive performance in patients one year after coronary artery bypass surgery. The current study reinvestigated this relation in a larger and more heterogeneous group--90 cardiac patients six months after cardiopulmonary bypass--using a more extensive checklist of subjective complaints and different neuropsychological tests. In agreement with previous research, the patients who reported complaints in specific cognitive areas were not found to have impaired cognitive functions as assessed with appropriate neuropsychological tests. The patients who reported deterioration in cognition after surgery were found to have higher levels of depression and state anxiety. These differences were significant for almost all evaluated cognitive functions. An alternative explanation of the relationship between mood and cognitive complaints based on personality traits, i.e., neuroticism, is offered.

Personality change following head injury: assessment with the NEO Five-Factor Inventory.

We evaluated personality change following head injury in 68 patients at 6 months postinjury using the NEO Five-Factor Inventory to assess the five personality dimensions of the Five-Factor Model of Personality. All items had to be rated twice, once for the preinjury and once for the current status. Twenty-eight trauma patients with injuries to other parts of the body than the head were used as controls. For the head-injured group, 63 relatives also completed the questionnaire. The results showed no differences between the ratings of head-injured patients and the ratings of trauma control patients. Both groups showed significant change in the personality dimensions Neuroticism, Extraversion, and Conscientiousness. Compared to their relatives, head-injured patients report a smaller change in Extraversion and Conscientiousness. Changes were not reported on the Openness and Agreeableness scales, by neither the head-injured or their relatives, nor by the trauma controls.

Short-term and long-term neuropsychological consequences of cardiac surgery with extracorporeal circulation.

OBJECTIVE: Cognitive dysfunction after extracorporeal circulation is a major continuing problem in modern cardiac surgery. We designed this prospective study to update the incidence of postoperative neuropsychological changes after routine cardiopulmonary bypass (CPB) and to identify perioperative variables associated with these complications. METHODS: We assessed the patients with a comprehensive neuropsychological test battery 1 day before, 7 days after (n = 109) and 6 months after (n = 91) cardiopulmonary bypass. We used patients undergoing major vascular or thoracic surgery as a surgical control group (n = 20). RESULTS: Repeated measures multivariate analysis of variance (using surgical group as a between-subjects factor) on the group data revealed significant changes early after surgery compared with the preoperative performance (P = 0.001). The early changes are characterized by a significant decrease of visual attention and verbal memory performance (univariate F-tests, always P < 0.05). Cardiac patients showing cognitive impairment after cardiac surgery had lower preoperative ejection fractions (P = 0.014) and a more complicated medical history (P = 0.046). At 6-month follow-up, the patients performed significantly better than before surgery (P < 0.001). CPB patients showing persistent cognitive impairment at follow-up were significantly older at the time of surgery (P = 0.005). Individual comparisons revealed that 45% of the patients undergoing CPB showed evidence of cognitive impairment soon after surgery. In 12% of the patients, the cognitive sequelae persisted at follow-up. Both group data and individual incidence rates revealed neither significant pre-post differences between the surgical groups nor a time-by-group interaction effect. Variables directly associated with CPB were not significantly associated with the occurrence of cognitive impairment after surgery. CONCLUSIONS: We conclude that an important proportion of the cognitive impairment after cardiac surgery is likely to be due to nonspecific effects of surgery.

Patients with psychiatric emergencies transported by an ambulance in an urban region.

This paper studies the use of an ambulance service in the case of psychiatric emergency referrals. A cross-sectional design was used to compare the patients brought in by an ambulance with all other psychiatric emergency referrals. The sociodemographic and clinical characteristics as well as the referral pattern of both groups of patients are compared. Results show that an important proportion of patients brought in by an ambulance can be described as high risk referrals. However, for another group of referrals the ambulance is used for other reasons. The possibility of using alternative social services in these cases are discussed.

Repeated psychiatric referrals to Belgian emergency departments: a survival analysis of the time interval between first and second episodes.

Repetition of psychiatric emergency department use by a relatively small number of patients constitutes a major problem for clinicians and service providers. This study aimed at the identification of risk factors for repetition by addressing the time interval between the first and second visits to the emergency department. The purpose was to investigate what patient characteristics and referral circumstances determine this interval. Over a two year period, data on all psychiatric emergency referrals to the emergency department of four public hospitals were collected with a standardized form. Data collected during the index referral of all patients were used for estimating the risk for repetition using survival analysis techniques. A large proportion of repeaters revisits the emergency department within a short time interval. Younger, male patients who present themselves spontaneously are more likely to repeat than others. Previous inpatient service use and the presence of a diagnosis of substance abuse disorder or psychotic disorder at the first visit further increases the risk for repetition. Previous service use and, to a lesser degree, demographic and clinical characteristics of psychiatric patients are useful in the prediction of variations in time between first and second referrals to the emergency department.

Short-term outcome following referral to a psychiatric emergency service.

The study described here is part of an evaluation of a pilot project concerning the implementation of three psychiatric crisis units in general hospitals in Belgium. The purpose was to evaluate the short-term outcome of a multidisciplinary crisis intervention for psychiatric patients referred to the emergency department. Patients were assessed with the General Health Questionnaire (GHQ-28) at the time of referral to the emergency department and again 1 month later. Patients referred for a psychiatric crisis intervention were compared with patients receiving short-term psychiatric inpatient treatment in another hospital. Patients referred to the emergency department showed a considerable degree of psychiatric disturbance. The General Health Questionnaire appeared to be a good measure for assessment of the "state" aspect of a psychiatric disturbance. The state of distress was significantly reduced one month after referral in both treatment conditions. Nevertheless, an important proportion of patients remained in a state of considerable distress. The results indicate that a short hospital-based crisis intervention approach is comparable with more traditional acute inpatient treatment. However, in the case of more severely distressed patients it may be insufficient. Several limitations of this study are also discussed (risk of overestimation of improvement, influence of time or pre-existing differences).

Epidemiology of psychiatric emergency referrals in four regions of Belgium.

Over a period of two years, all psychiatric emergency referrals at the emergency department of four public hospitals were monitored using a standardized form. The results showed that the hospitals share a typical profile of the psychiatric emergency department user. The profile is consistent with earlier descriptive studies, in Belgium as well as in other countries. Possible ways to overcome problems with data collection within the setting of a psychiatric emergency department are suggested. Finally, the necessity of monitoring the service needs of specific subgroups is discussed.

Recent changes in the age- and gender-specific rates of attempted suicide in Gent.

The gender-specific rate of attempted suicide, calculated from hospital admission data, was significantly lower in 1990 than in 1986 in females and, when age is taken into account, in females younger than 35 and in males younger than 25 years. The incidence of suicide attempts seen by general practitioners also decreased. Indications for rejection of the artefact hypothesis as explanation for this decrease have been investigated. It was shown that the decrease in the prevalence was found at local and national levels and was not the result of a decrease in referrals to general hospitals. Moreover, the decrease in the rate was associated with an increase in the use of outpatient mental health facilities in females and with a trend to increase in the 15-24 age group. The number of suicide attempts referred by Community Mental Health Services to the general hospital and the suicide rate in out-patients remained constant during the study period. The findings do not support the artefact hypothesis but indicate that there was a real decrease in the rate of attempted suicide. Moreover, the findings suggest that out-patient treatment can be efficacious in the primary prevention of suicidal behaviour.

Levodopa addiction. A case study.

A case is presented of a young woman with a serious addiction to levodopa who over the years developed an extrapyramidal syndrome and chronic paranoid psychotic behaviour. The possible pathophysiological mechanism is discussed.

Effect of asymptomatic carotid artery disease on cognitive outcome after cardiopulmonary bypass.

This prospective study reinvestigates the effect of asymptomatic carotid artery disease on the cognitive outcome after cardiopulmonary bypass (CPB) (Harrison et al., 1989). Patients (N = 104) scheduled for cardiac surgery using CPB were classified in one of two groups based on the results of a preoperative duplex B mode Doppler scan of the internal carotid arteries. All patients received a neuropsychological examination before surgery, 8 days after surgery, and 6 months after surgery (n = 79). When group data are considered, patients showed evidence of selective cognitive dysfunction early after surgery. These dysfunctions were resolved by the sixth postoperative month. We found no indications that the presence of asymptomatic carotid artery disease increased the incidence of cognitive disturbances after CPB or differentially affected the postoperative performance. We conclude that mild to moderate asymptomatic carotid artery disease does not appear to play a major role in the genesis of postoperative neuropsychological sequelae.

Neuropsychological impairment in candidates for cardiac surgery.

The preoperative cognitive test performance of 77 candidates for elective open-heart surgery that did not suffer from carotid artery stenosis, was compared with the performance of 37 normal controls. Multivariate analysis of variance, with state anxiety score and depression score as covariates, showed a significantly reduced cognitive performance in the surgical candidates. Post hoc analyses using univariate F tests revealed a significantly impaired word fluency, manual dexterity, verbal learning, and psychomotor speed. A stepwise multiple regression analysis revealed that, besides the usual demographic factors, preoperative variables indicating a more precarious heart function also contributed significantly to the estimation of the proportion of variance of the results on several impaired cognitive tests. Future research should focus on the etiology of the cognitive impairment in cardiovascular disease.

Strategies to increase compliance with out-patient aftercare among patients referred to a psychiatric emergency department: a multi-centre controlled intervention study.

BACKGROUND: Compliance with referral for out-patient aftercare of psychiatric emergency patients is limited. This study investigated the efficacy of a combination of several referral strategies (fixed appointment, involvement of the family, presence of the aftercare person, motivational counselling) in increasing referral and treatment compliance of patients referred to the psychiatric emergency department of three general hospitals. METHODS: A randomized controlled design was used to assess the effect of this experimental condition on referral compliance and on continuation of aftercare treatment. RESULTS: A significant beneficial effect on compliance with the referral was found in two hospitals and a near-significant effect in the third. After 3 months of aftercare, the influence of the experimental procedure on adherence to therapy was still significant in two hospitals, but not in the third. CONCLUSIONS: Helping the patient to attend an initial appointment can be achieved by a combination of practical and organizational arrangements.

Course of neuropsychological recovery from moderate-to-severe head injury: a 2-year follow-up.

Neuropsychological outcome and recovery of a group of 91 patients with moderate-to-severe head injuries were prospectively investigated over a 2 year period, with evaluations at acute hospital discharge at 6 months and 2 years post-injury. A group of 39 trauma patients with injuries to parts of the body other than the head were used as controls. The head injured group performed significantly worse than the control group at baseline, 6 months and 2 years post-injury. Significant improvement was found during the first 6 months, but also between 6 months and 2 years post-injury. Trauma controls also performed significantly better at 6 months post-injury compared to baseline. Differential practice effects between groups cause difficulties in determining recovery. Within the head injured group, three distinct recovery groups were identified varying as a function of coma-length and coma-duration. The first group is comparable with the trauma controls. The other two groups demonstrate significant neuropsychological impairments at baseline, with one group showing a marked improvement over the 2 year period, and the other group showing only small improvement over this time period.

Spectrum analysis of the EEG in schizophrenic patients.

A method is presented for the harmonic analysis of the human EEG. Its use for the study of schizophrenic patients under phenothiazine treatment is discussed and some examples are given. Correlations are observed with clinical evolution and plasma level of the drugs.

Subjective complaints versus neuropsychological test performance after moderate to severe head injury.

Neuropsychological test performance and subjective complaints of 85 patients with moderate to severe head injury were investigated at 6 months postinjury. The neuropsychological test battery included 10 measures of attention, memory, mental flexibility, reaction time, visuoconstruction and verbal fluency. Subjective complaints were assessed using a self-report questionnaire subdivided into four subscales (somatic, cognitive, emotional and behavioural). Ratings were obtained for the pre-injury and current status. Thirty-three trauma patients with injuries to other parts of the body than the head were used as controls. For the head injured, relatives also completed the questionnaire. Head injured patients performed significantly below trauma control patients on nearly all test measures. Head injured patients and their relatives reported a significant increase in subjective complaints since the injury on all four subscales, with no differences between patients' and relatives' reports. These changes were also reported by the trauma controls, but they report fewer changes in somatic and cognitive functioning. Exploratory canonical correlation analyses revealed no correlations between any of the four scales of the questionnaire and the test measures, nor for the head injured, the trauma controls, or the relatives, indicating no relevant relationship between subjective complaints and neuropsychological test performance.