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Biomedical subjects

A Rupp

Publications and source records attributed to A Rupp.

At least 19 recordsLinked to original sources

Is frontal lobe involved in the generation of auditory evoked P50?

This study examined the functional substrate of P50 suppression. Auditory evoked potentials (AEPs) and magnetic fields (AEFs) were recorded from healthy subjects simultaneously and analyzed using spatio-temporal source analysis. The resulting equivalent dipole model for the AEP consisted of one source in the auditory cortex (AC) of each hemisphere and an radially oriented medial frontal source, both with maximum AEP activity around 50 ms. The frontal source was functionally separated from the AC sources since it peaked significantly later and showed significantly larger P50 amplitude suppression. P30m showed neither suppression nor substantial frontal activity. In sum, this study relates P50 suppression to reduction of AC source activity and is the first to yield direct evidence for frontal involvement in P50 suppression.

Acoustic Stimulation↗

Interaction of tactile input in the human primary and secondary somatosensory cortex--a magnetoencephalographic study.

Interaction of simultaneous tactile input at two finger sites in primary (SI) and secondary somatosensory cortex (SII) was studied by whole-head magnetoencephalography. Short pressure pulses were delivered to fingers of the right and left hand at an interstimulus interval of 1.6 s. The first phalanx of the left digit 1 and four other sites were stimulated either separately or simultaneously. We compared four sites with increasing distance: the second phalanx of left digit 1, left digit 5, and digits 1 and 5 of the right hand. The temporal evolution of source activity in the contralateral SI and bilateral SII was calculated using spatiotemporal source analysis. Interaction was assessed by comparing the source activity during simultaneous stimulation with the sum of the source activities elicited by separate stimulation. Significant suppressive interaction was observed in contralateral SI only for stimuli at the same hand, decreasing with distance. In SII, all digits of the same and the opposite hand interacted significantly with left digit 1. When stimulating bilaterally, SII source waveforms closely resembled the time course of the response to separate stimulation of the opposite hand. Thus, in bilateral simultaneous stimulation, the contralateral input arriving first in SII appeared to inhibit the later ipsilateral input. Similarly, the separate response to input at two unilateral finger sites which arrived slightly earlier in SII dominated the simultaneous response. Our results confirm previous findings of considerable overlap in the cortical hand representation in SII and illustrate hemispheric specialization to contralateral input when simultaneous stimuli occur bilaterally.

Adult↗

Variability of blood-brain ratios of phenylalanine in typical patients with phenylketonuria.

Blood-brain ratios (BBR) of phenylalanine (Phe) were determined by quantitative in vivo 1H magnetic resonance spectroscopy (1H-MRS) in 17 adult patients with early-treated phenylketonuria who were randomly selected from a sample of 75 adults. Measurements were performed in all patients during steady-state conditions. The BBR showed a unimodal distribution with a mean of 4.0 (range 3.3 to 4.5). Blood-brain ratios were comparable for subgroups of patients with genotypes classified as severe, moderate, or mild and for patients on different types of diets. Brain Phe concentrations showed a strong linear correlation with blood Phe values (r = 0.93, P < 0.001). There were no saturation effects for blood Phe values up to 1.8 mmol/L, and a local regression analysis did not confirm increasing BBR for increasing blood Phe values. The intellectual outcome (Wechsler Adult Intelligence Scale) was correlated with long-term dietary control (r = -0.65, P < 0.05), fluctuation of blood Phe values during treatment (r = -0.60, P < 0.05), and concurrent blood and brain Phe concentration. The severity of white matter changes visible on magnetic resonance images (MRI) was increased with high blood and brain Phe concentrations but failed to reach statistical significance. No correlation was found between BBR values, intelligence quotient, and MRI grade. Based on the assumption that BBR show intraindividual stability, the current data do not support the hypothesis that blood-brain barrier transport of Phe is a key explanatory factor for outcome variability in the vast majority of "typical" patients with phenylketonuria.

Adolescent↗

Managed care and children's behavioral health services in Massachusetts.

OBJECTIVE: The authors investigated changes in treatment patterns and costs of care for children after the implementation of the Massachusetts Medicaid carve-out managed care plan. METHODS: The authors hypothesized that after the introduction of managed care, per-child expenditures would be reduced, continuity of care would not improve, and per-child mental health expenditures would undergo larger reductions for disabled children, compared with children enrolled in the Aid to Families With Dependent Children program. Using data from Medicaid and the Massachusetts Department of Mental Health, the authors studied 16,664 Massachusetts Medicaid beneficiaries aged one to 17 years for whom reimbursement claims were submitted for psychiatric or substance use disorder treatment at least once during the two years before the introduction of managed care (1991 to 1992) or during the two years afterward (1994 to 1995). Multivariate analysis was used to estimate changes in probability of admission, and, among patients admitted, to identify factors accounting for variation in length of stay. To assess the variation in expenditures, we regressed the same variables, using the natural logarithm function to transform total mental health expenditures data and inpatient expenditures data to reduce skewness. RESULTS: After the introduction of managed care, per-child expenditures were lower, especially for disabled children, and the Department of Mental Health was used as a safety net for the most seriously ill children without increasing state expenditures. Continuity of care appeared to decline for disabled children. CONCLUSIONS: It is likely that a combination of factors related to the reported changes in patterns of care and expenditures were responsible for the overall per-child expenditures.

Adolescent↗

Fast temporal interactions in human auditory cortex.

The temporal resolution of the human primary auditory cortex (AC) was studied using middle-latency evoked fields. Paired sounds with either the same or different spectral characteristics were presented with gaps between the sounds of 1, 4, 8 and 14 ms. Spatio-temporal modelling showed (1) that the response to the second sound was recognizable with gaps of 1 ms and rapidly increased in amplitude with increasing gap durations, (2) an enhanced N40m amplitude at gaps > 4 ms, (3) delayed N19m-P30m latencies when the stimuli were different. The median psychoacoustical thresholds were 1.6 ms for the same stimuli and 2.5 ms for different stimuli, confirming the electrophysiological evidence for rapid pattern-specific temporal processing in human primary auditory cortex.

Acoustic Stimulation↗

Magnetic source imaging of tactile input shows task-independent attention effects in SII.

We investigated whether attention to different stimulus attributes (location, intensity) has different effects on the activity of the secondary (SII) somatosensory cortex. Tactile stimuli were applied to the left index finger and somatosensory evoked fields (SEFs) were recorded using a whole-head magnetoencephalography (MEG) system. Two oddball paradigms with stimuli varying in location or intensity were performed in an ignore and an attend condition. Brain sources were estimated by magnetic source imaging. No attention effect was observed for the primary SI area. However, attention enhanced SII activity bilaterally from 55 to 130 ms by 52% in the spatial and 64% in the intensity discrimination task. SII attentional enhancement was very similar in both paradigms and occurred both for deviants and standards.

Adult↗

Deconvolution of 40 Hz steady-state fields reveals two overlapping source activities of the human auditory cortex.

Steady-state auditory evoked fields were recorded from 15 subjects using a whole head MEG system. Stimuli were 800 ms trains of binaural clicks with constant stimulus onset asynchrony (SOA). Seven different SOA settings (19, 21, 23, 25, 27, 29 and 31 ms) were used to give click rates near 40 Hz. Transient responses to each click were reconstructed using a new algorithm that deconvoluted the averaged responses to the different trains. Spatio-temporal multiple dipole modelling in relation to 3D MRI scans revealed two overlapping source components in both the left and right auditory cortex. The primary sources in the medial part of Heschl's gyrus exhibited a N19-P30-N40 m pattern. The secondary, weaker sources at more lateral sites on Heschl's gyrus showed a N24-P36-N46 m pattern. When applied to transient middle latency auditory evoked fields (MAEFs) recorded at SOAs of 95-135 ms, the primary sources imaged activities similar to the deconvoluted steady-state responses, but the secondary source activities were inconsistent. Linear summation of the deconvoluted source waveforms accounted for more than 96% of the steady-state variance. This indicates that the primary activity of the auditory cortex remains constant up to high stimulation rates and is not specifically enhanced around 40 Hz.

Acoustic Stimulation↗

New signs characteristic of myocardial bridging demonstrated by intracoronary ultrasound and Doppler.

BACKGROUND: Large discrepancies exist concerning the incidence of myocardial bridging. This has been reported to be 0.5%-2.5% following coronary angiography but 15%-85% following autopsy. The purpose of the study was to use intravascular ultrasound and intracoronary Doppler to study the morphology and flow characteristics of myocardial bridging in order to find feasible parameters of this syndrome. METHODS AND RESULTS: Intravascular ultrasound was performed in 62/69 patients in whom typical angiographic 'milking effects' were present. In 48 patients, intracoronary Doppler was performed. A specific, echolucent 'half moon' phenomenon surrounding the myocardial bridge was found in all the patients. The thickness of the half moon area was 0.47 +/- 0.19 mm in diastole and 0.52 +/- 0.23 mm in systole. There was systolic compression of the myocardial bridge with a lumen reduction during systole of 36.4 +/- 8.8%. Using intracoronary Doppler, a characteristic early diastolic 'finger tip' phenomenon was observed in 42 (87%) of the patients. All patients showed no or reduced antegrade systolic flow. Coronary flow velocity reserve was 2.03 +/- 0. 54. After intracoronary nitroglycerin injection, retrograde systolic flow occurred in 37 (77%) of the 48 patients, with a velocity of -22. 2 +/- 13.2 cm. s(-1). Intravascular ultrasound revealed atherosclerotic involvement of the proximal segment in 61 (88%) of the 69 patients, with an area stenosis of 42 +/- 13%. No plaques were found in the bridge or distal segments in the 62 patients in whom it was possible to introduce the ultrasound catheter throughout the bridging segment. CONCLUSION: Myocardial bridging is characterized by the following morphological and functional signs: a specific, echolucent half moon phenomenon over the bridge segment, which exists throughout the cardiac cycle; systolic compression of the bridge segment of the coronary artery; accelerated flow velocity at early diastole (finger-tip phenomenon); no or reduced systolic antegrade flow; decreased diastolic/systolic velocity ratio; retrograde flow in the proximal segment, which is provoked and enhanced by nitroglycerin injection.

Blood Flow Velocity↗

Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria.

Large neutral amino acids (LNAAs), including phenylalanine (Phe), compete for transport across the blood-brain barrier (BBB) via the L-type amino acid carrier. Accordingly, elevated plasma Phe impairs brain uptake of other LNAAs in patients with phenylketonuria (PKU). Direct effects of elevated brain Phe and depleted LNAAs are probably major causes for disturbed brain development and function in PKU. Competition for the carrier might conversely be put to use to lower Phe influx when the plasma concentrations of all other LNAAs are increased. This hypothesis was tested by measuring brain Phe in patients with PKU by quantitative 1H magnetic resonance spectroscopy during an oral Phe challenge with and without additional supplementation with all other LNAAs. Baseline plasma Phe was approximately 1,000 micromol/l and brain Phe was approximately 250 micromol/l in both series. Without LNAA supplementation, brain Phe increased to approximately 400 micromol/l after the oral Phe load. Electroencephalogram (EEG) spectral analysis revealed acutely disturbed brain activity. With concurrent LNAA supplementation, Phe influx was completely blocked and there was no slowing of EEG activity. These results are relevant for further characterization of the LNAA carrier and of the pathophysiology underlying brain dysfunction in PKU and for treatment of patients with PKU, as brain function might be improved by continued LNAA supplementation.

Adult↗

Neurological outcome in adult patients with early-treated phenylketonuria.

UNLABELLED: Due to the observation of severe neurological symptoms in single patients as well as brain imaging, neuropsychological and neurophysiological abnormalities, the long-term prognosis of treated phenylketonuria is still under discussion. We investigated the neurological outcome of 57 (24 male, 33 female) patients with phenylketonuria (diet onset < 3 months) at a mean age of 23.6 (17-33) years in comparison to control subjects. Methods used were a clinical-neurological examination, tests for fine motor abilities, IQ test (WAIS-R), a neuropsychological attention task and MRI (30 patients only). Tremor was increased in the patients (28%) compared to controls (15%). Fine motor abilities were significantly reduced in three areas: hand-wrist steadiness, finger-hand dexterity and hand-wrist speed. Tremor as well as reduced fine motor skills were not associated with treatment-related variables, e.g. diet onset, strictness of biochemical control or amount of MRI white matter change. IQ was lower in patients (mean 97.6) compared to matched control subjects (mean 105.5). IQ at 12 years was correlated with biochemical control from birth up to the age of 12 and remained stable up to adult age, independent of biochemical control after 12 years of age. In contrast to the other outcome parameters, the performance in a neuropsychological attention task was influenced by the concurrent plasma phenylalanine concentration. Specific late-onset neurological impairment was not identified in this sample of early-treated adults with phenylketonuria. CONCLUSION: Careful neurological investigation revealed subtle symptoms of brain damage even after early-initiated treatment in adult patients with phenylketonuria. At present it cannot be excluded that further neurological deterioration could emerge later in life. Thus, patients with phenylketonuria - either on or off diet - should be monitored throughout life.

Adolescent↗

Neuropsychologic functions of early treated patients with phenylketonuria, on and off diet: results of a cross-national and cross-sectional study.

Twenty-two French patients with early treated phenylketonuria (PKU) off diet (no reduced phenylalanine, Phe) since their 5th birthday, 23 German patients on diet (reduced Phe), and 21 healthy control subjects from childhood to adulthood matched for age, sex, and IQ were investigated for visuomotor reaction time, sustained attention, and visual stimulus scanning. Determinations were made whether 1) the three groups showed different developmental trends in their reaction times, 2) the threshold of a Phe blood level of 360 mumol/L formulated in recent recommendations can be regarded as safe, 3) test performances are related to the quality of dietary control in the same way for all age groups, and 4) long-term elevated Phe levels result in aggravating effects of increasing differences between patients on and off diet and healthy controls. Results revealed that developmental trends were similar in all treatment groups. Only children with a mean Phe level below 360 mumol/L performed as well as control subjects. Differences between treatment groups decreased in adulthood, and no aggravating effect could be observed. Mean performance of patients with mild PKU off diet was in the same range as performance of patients with classical or mild PKU on diet, calling into question the benefit of treating these patients. It is concluded that it is preferably safer to maintain Phe blood levels below 360 mumol/L at least during the first 10 y of life.

Adolescent↗

Solutions for adverse selection in behavioral health care.

Health plans have incentives to discourage high-cost enrollees (such as persons with mental illness) from joining. Public policy to counter incentives created by adverse selection is difficult when managed care controls cost through methods that are largely beyond the grasp of direct regulation. In this article, the authors evaluate three approaches to dealing with selection incentives: risk adjustment, the carving out of benefits, and cost- or risk-sharing between the payer and the plan. Adverse selection is a serious problem in the context of managed care. Risk adjustment is not likely to help much, but carving out the benefit and cost-sharing are promising directions for policy.

Economic Competition↗

Phenylalanine hydroxylase genotypes, predicted residual enzyme activity and phenotypic parameters of diagnosis and treatment of phenylketonuria.

The interdependence of the predicted in vitro residual enzyme activity (PRA), as deduced from the complete genotypes of 64 hyperphenylalaninaemic patients, and parameters for diagnosis of hyperphenylalaninaemic disorders, the fluctuation of the phyenlylalanine (Phe) values during treatment, long-term dietary control during treatment, and a parameter for the outcome of therapy (IQ) was investigated by correlation analysis. A highly significant correlation was found between the PRA and diagnostic parameters, as well as the fluctuation of the Phe values during treatment. Significant correlations were also observed between the parameter describing the fluctuation of the Phe values and the IQ, as well as between the quality of dietary control and IQ. The PRA is a valuable tool for the differential diagnosis of hyperphenylalaninaemic disorders and for the prediction of one aspect of the course of the disease which is related to the intellectual outcome of therapy. The quality of dietary control was independent of the genotype, indicating that the outcome of therapy can be successfully manipulated in spite of the genetic make-up.

Alleles↗

Psychosocial aspects in phenylketonuria.

Psychosocial aspects in phenylketonuric (PKU) patients are reported. In two separate studies patients with PKU differing in age (children versus adolescents), were assessed. The main message of the first prospective study on 58 10-year-old patients is that normally intelligent PKU patients who were treated early and strictly did not show a higher risk for severe emotional and behavioural maladjustment compared with healthy controls at the age of 10 years. The data were obtained in the course of the German PKU Collaborative Study by the "Personality Questionnaire for Children (PFK 9-14)". All patients received nutritional, medical, and psychological counselling every 6 months. In the second retrospective study, 34 early treated, normally intelligent adolescents with PKU (age: mean = 14.6, SD = 2.0, range = 11-18 years) and their mothers were assessed with several psychometric personality inventories and self-developed questionnaires concerning their psychosocial situation and their disease- and diet-specific knowledge. Using the Mannheimer Biographic Inventory (MBI), the Personality Questionnaire for Children (PFK 9-14), and the Freiburger Personality Inventory (FPI) the adolescent patients described their social life and their emotional development as being distinctly restricted. Their knowledge concerning disease and diet was alarmingly poor and the majority had great difficulties in satisfactory dietetic management without parental help. In addition to the burdensome diet, developmental crises like puberty may cause more frequently emotional and behavioural problems in PKU patients.

Adolescent↗

Intellectual development of the patients of the German Collaborative Study of children treated for phenylketonuria.

In a multicentric and interdisciplinary approach the German Collaborative Study of Children Treated for Phenylketonuria (PKU) investigates prospectively the effects of early started strict dietary treatment on the growth and development of 140 patients. The present paper focuses on longitudinal intelligence data from 4, 5 and 9 years of age of 89 patients in relation to the quality of dietary control in comparison to 200 healthy children tested by the same protocol. Cluster analysis of phenylalanine (Phe) levels distinguished a cluster of good dietary control with Phe levels according to the recommendation of maintaining Phe levels below 360 mumol/l, a cluster of poor dietary control with Phe levels greater than 600 mumol/l after the age of 3 years, and a cluster of intermediate control. Intelligence quotients (IQ) and Phe clusters were inversely related with non-significant differences between the clusters good and intermediate. On average, all three clusters scored significantly lower than healthy age peers. Mean IQ scores decreased for patients as well as for healthy children due to different tests used at different measurement occasions. Patients with poor dietary control showed a steeper decrease between 4 and 5 years than patients with better dietary control. Between 5 and 9 years IQ differences between patients and healthy children remained stable. Verbal IQs were higher than performance IQs for patients as well as for healthy children. It is concluded that after early and strict treatment during the pre-school years Phe levels, in the range observed, do not influence IQ development until the age of 9 years. IQ subscale pattern indicate that PKU results in a generalized reduction of IQ instead of disturbing specific abilities. It remains to be investigated whether higher Phe levels are also innocuous and/or may result in late effects.

Child↗

Long-term follow-up of patients treated for phenylketonuria (PKU). Results from the Prague PKU Center.

In order to examine the association between treatment parameters and intellectual outcome, a total of 58 adolescents with phenylketonuria (PKU) treated at the PKU center of the Department of Pediatrics at the University of Prague were tested at the age of 15 years with the Prague Child Wechsler Test. Patients were classified into three groups with different levels of dietary control that remained relatively stable over time at mean phenylalanine levels of 360, 540 and 680 mumol/l. The mean level of phenylalanine was highly correlated with IQ and school education. Patients with mean phenylalanine levels of < or = 360 mumol/l had near-normal level. Initial experience with eight cases of maternal PKU underlines the necessity for a strict treatment regimen, which must be started pre-conception in order to prevent the fetus from developmental damage.

Czech Republic↗

Effects of concurrent phenylalanine levels on sustained attention and calculation speed in patients treated early for phenylketonuria.

The effects of short-term and long-term phenylalanine (Phe) levels on sustained attention have been investigated in phenylketonuria (PKU) patients. Two studies, one cross-sectional with 103 patients aged 8.5-9.0 years, the other with 15 adult patients following an interventional design with experimentally manipulated concurrent Phe levels are reported. The effects of concurrent Phe levels separated from long-term Phe control on sustained attention and calculation speed in simple addition tasks were investigated. Children with low concurrent Phe levels performed significantly better than children with high concurrent Phe levels when long-term dietary control was good but not when long-term control was poor. Adult PKU patients with high concurrent Phe levels showed significantly longer reaction times and lower speed in calculation than a healthy control group. Deficits were partly reversible by lowering the concurrent Phe level over a period of 4-5 weeks. The results demonstrated the impact of concurrent Phe level on neuropsychological functioning in childhood as well as in adulthood.

Adolescent↗