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Biomedical subjects

H J Berger

Publications and source records attributed to H J Berger.

At least 19 recordsLinked to original sources
PubMed2001

Cognitive styles in high-functioning adolescents with autistic disorder.

This study addressed the operationalization, the identification, and the prevalence of weak central coherence and poor cognitive shifting in 35 high-functioning adolescents with autism. Central coherence and cognitive shifting were represented by two factors in a factor analysis, each reflecting a constituent aspect of the domain in question. With regard to central coherence, these aspects were the ability of piecemeal processing and the ability to process meaning. The aspects related to cognitive shifting concerned internally and externally controlled shifting. Weak central coherence and poor cognitive shifting did not appear to be related to measures of symptom severity, social understanding, and social competence. Both these cognitive styles did not appear to be universal to autism. In our sample, weak central coherence and poor cognitive shifting were found to be significantly more common than in normative control subjects.

Adolescent↗
PubMed2001

Intravenous safety and pharmacokinetics of a novel dimerizer drug, AP1903, in healthy volunteers.

AP1903 is a novel gene-targeted drug that is being developed for use in drug-regulated cell therapies. An intravenous, single-blind, placebo- and saline-controlled, ascending-dose study was performed to evaluate the safety, tolerability, and pharmacokinetics of AP1903. Twenty-eight normal healthy male volunteers were randomized into five dosage groups of AP1903 (0.01, 0.05, 0.1, 0.5, and 1 mg/kg). Within each group, 4 volunteers received a single dose of AP1903, 1 volunteer received an equal volume of placebo, and 1 received an equal volume of normal saline. The only exception was in the 0.5 mg/kg group, in which 4 volunteers were dosed: 3 received AP1903 and 1 received normal saline. All dosages were administered as intravenous infusions over 2 hours. Clinical safety parameters were monitored, and serial blood and urine samples were collected for analysis of AP1903. No drug-related adverse events were observed at any of the dose levels with the possible exception of facial flushing in 1 volunteer at the 1.0 mg/kg dose level. AP1903 plasma levels were directly proportional to the administered dose, with mean Cmax values ranging from approximately 10 to 1,275 ng/mL over the 0.01 to 1.0 mg/kg dose range. Following the infusion period, blood concentrations revealed a rapid distribution phase, with plasma levels being reduced to approximately 18%, 7%, and 1% of the maximal concentration at 0.5, 2, and 10 hours postdose, respectively. AP1903 was shown to be safe and well tolerated at all dose levels and demonstrated a favorable pharmacokinetic profile at doses well above the anticipated therapeutic dose.

Adult↗
PubMed1999

Relationship between memory strategies and motor symptoms in Parkinson's disease.

Patients with Parkinson's disease(PD) show a serious decrease in performance on tasks which lack explicit guidelines and which necessitate the subject to develop his or her own strategy. Using the California Verbal Learning Task(CVLT) we have found evidence that this phenomenon becomes also manifest in learning and memory. The goal of the present study on PD was to investigate whether or not there is an intrinsic relationship between PD-specific deviant learning characteristics and the severity of motor symptomatology. The results show, as expected, a significant correlation between the severity of bradykinetic/hypokinetic symptoms and the serial clustering gradient of the CVLT: the more bradykinetic PD patients (n = 48) were, the more they were dependent on the externally guided serial learning strategy. The findings are discussed in the context of our hypothesis that the actual deficit in patients with PD is a deficient processing of ambiguous internal cues.

Cluster Analysis↗
PubMed1998

[Cognitive deficits in Parkinson's disease].

In neuropsychological studies of Parkinson's disease, cognitive deficits are frequently reported, but the nature of these deficits is not clear. As far as cognitive deficits are manifest in parkinsonian patients at an early stage of the disease, many studies tend to describe them as fitting a frontal syndrome. As a consequence of dysfunction of the striatum, the (pre)frontal cortex receives deficient input from the striatum, which might explain the similarity of the cognitive deficits of parkinsonian patients with those of patients with frontal dysfunction. The present studies provide evidence that the cognitive deficits of parkinsonian patients display a certain similarity with those of patients with frontal dysfunction at the level of the ultimate performance, but that the underlying processes have a distinct character. Parkinsonian patients exhibit a decrease in self-generated problem-solving. This deficit is manifest at a level of cognitive function, which goes beyond task or domain. Among all disease variables, only severity of the disease and especially rigidity proved to be related consistently to this decrease in self-generated problem-solving.

Adult↗
PubMed1997

Symptoms and duration of the prodromal phase in Parkinson's disease.

To investigate the duration of a prodromal phase before the onset of the classic symptoms of idiopathic Parkinson's disease, the authors conducted a retrospective case-control study of 60 patients with Parkinson's disease and 58 age- and sex-matched control subjects, covering the decade preceding the onset of classic Parkinson's disease. The symptoms were derived from files of the patients' general practitioners. Compared with control subjects, patients pre-Parkinson's disease had more central nervous system, psychologic, musculoskeletal, and cardiovascular (i.e., autonomic) symptoms. Patients pre-Parkinson's disease also made more visits to general practitioners and medical specialists. The results indicate that the onset of classic parkinsonism is frequently preceded by a prodromal phase lasting from 4-6 years.

Adult↗
PubMed1996

Role of transiently altered sarcolemmal membrane permeability and basic fibroblast growth factor release in the hypertrophic response of adult rat ventricular myocytes to increased mechanical activity in vitro.

One of the trophic factors that has been implicated in initiating or facilitating growth in response to increased mechanical stress in several tissues and cell types is basic fibroblast growth factor (bFGF; FGF-2). Although mammalian cardiac muscle cells express bFGF, it is not known whether it plays a role in mediating cardiac adaptation to increased load, nor how release of the cytosolic 18-kD isoform of bFGF would be regulated in response to increased mechanical stress. To test the hypothesis that increased mechanical activity induces transient alterations in sarcolemmal permeability that allow cytosolic bFGF to be released and subsequently to act as an autocrine and paracrine growth stimulus, we examined primary isolates of adult rat ventricular myocytes maintained in serum-free, defined medium that were continually paced at 3 Hz for up to 5 d. Paced myocytes, but not nonpaced control cells, exhibited a "hypertrophic" response, which was characterized by increases in the rate of phenylalanine incorporation, total cellular protein content, and cell size. These changes could be mimicked in control cells by exogenous recombinant bFGF and could be blocked in continually paced cells by a specific neutralizing anti-bFGF antibody. In addition, medium conditioned by continually paced myocytes contained significantly more bFGF measured by ELISA and more mitogenic activity for 3T3 cells, activity that could be reduced by a neutralizing anti-bFGF antibody. The hypothesis that transient membrane disruptions sufficient to allow release of cytosolic bFGF occur in paced myocytes was examined by monitoring the rate of uptake into myocytes from the medium of 10-kD dextran linked to fluorescein. Paced myocytes exhibited a significantly higher rate of fluoresceinlabeled dextran uptake. These data are consistent with the hypothesis that nonlethal, transient alterations in sarcolemmal membrane permeability with release of cytosolic bFGF is one mechanism by which increased mechanical activity could lead to a hypertrophic response in cardiac myocytes.

Animals↗
PubMed1996

Executive functions and disease characteristics in Parkinson's disease.

In the present study, we investigated the association of two executive functions with disease characteristics in Parkinson's disease (PD), especially with severity of motor symptoms. We operationalized two executive functions, viz. fluency and cognitive shifting, each in a number of tests with heterogeneous materials, but with an identical format. We calculated the correlations between test performance and disease characteristics, including the factor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). The results of this study show that only cognitive shifting was consistently associated with the severity of motor symptoms in PD, in particular with rigidity. None of the fluency tests had a significant association with severity of motor symptoms. The present study indicates that PD, as reflected by the severity of motor symptoms, is not associated with a general decrease in executive function. In spite of the fact that both are executive functions and both require generation of items, fluency and cognitive shifting are differentially related to PD.

Aging↗
PubMed1996

Memory performance under varying cueing conditions in patients with Parkinson's disease.

The present study is a continuation of a previous study in memory performance which showed that Parkinson's disease (PD) patients increasingly relied on explicit cues which prompt the external strategy of serial clustering, in comparison to control subjects (CS), who profited increasingly from implicit cues which prompt the internal and more effective strategy of semantic clustering. In this study, we investigated whether the recall of PD patients can be affected by adding or removing explicit cues. We manipulated the California Verbal Learning Test in two ways. First, we told the subjects under study in advance from which categories the items to be recalled were derived, thus making the implicit cue to cluster semantically explicit (explicit condition). Next, we permuted the sequence of the items in each trial, thus preventing the subjects from adhering to the serial order, i.e. to explicit cues (permuted condition). We included the data of our previous study (mixed condition) in the analysis of memory and learning performance in the three conditions. Learning of PD patients, as reflected in the semantic ratio, proved to be more affected by the cueing conditions than that of CS. Total performance and the serial ratios did not show a significant interaction between group and cueing condition. The results are discussed in terms of external and internal generation of problem-solving strategies.

Adult↗
PubMed1995

Card sorting performance in Parkinson's Disease: a comparison between acquisition and shifting performance.

In the present study we tested the hypothesis that learned irrelevance underlies the frequently observed poor performance of Parkinson's disease (PD) patients on card sorting tests. If learned irrelevance accounts for the poor performance of PD patients on card sorting tests, PD patients and control subjects (CS) will not differ in the acquisition phase, during which basic concept formation is assessed, but they will differ in the subsequent shifting phases. We presented three distinct card sorting tests with an identical format to 51 PD patients and 24 normal controls. The groups did not differ with respect to intelligence, memory, or attention. PD patients showed a slightly better performance in the acquisition phase. In the first shifting phase, the performance of PD patients was significantly poorer than that of control subjects after correction for basic concept formation. In the second shifting phase this difference disappeared. We conclude that learned irrelevance does not account for the poor performance of PD patients in card sorting tests. The results are discussed in terms of self-generation of problem solving strategies.

Age of Onset↗
PubMed1994

Memory and learning strategies in patients with Parkinson's disease.

Parkinson's disease patients (PD) do not differ from control subjects (CS) when they have to execute a problem solving task in which external cues for solving the problem are given. However, when PD have to solve a problem by means of an internally generated strategy, they show a serious decrease in performance. We hypothesised that this distinction may also apply to the way PD and CS organize recall. In order to test our hypothesis the California Verbal Learning Test (CVLT) was administered to 59 PD and 30 CS. The test consists of five learning trials using a 16-word target list, composed of four items from each of four semantic categories. The fact that the word list was built on this implicit organization was not divulged in advance. The sequence in which the words were read is fixed; each subsequent word belongs to a category being different from the category to which the preceding word belongs. The organization in recall according to the semantic categories is considered to be the result of an unprompted, internally generated strategy. Recall according to the sequence in which the words are read by the experimenter, is viewed as an externally offered strategy. The results prove to be in line with our hypothesis: unlike CS who appeared to rely mainly and increasingly on an internally generated semantic organization, PD showed evidence of gradually adhering more to the externally imposed serial sequence.

Aged↗
PubMed1994

Continual electric field stimulation preserves contractile function of adult ventricular myocytes in primary culture.

To model with greater fidelity the electromechanical function of freshly isolated heart muscle cells in primary culture, we describe a technique for the continual electrical stimulation of adult myocytes at physiological frequencies for several days. A reusable plastic cover was constructed to fit standard, disposable 175-cm2 tissue culture flasks and to hold parallel graphite electrodes along the long axis of each flask, which treated a uniform electric field that resulted in a capture efficiency of ventricular myocytes of 75-80%. Computer-controlled amplifiers were designed to be capable of driving a number of flasks concurrently, each containing up to 4 x 10(6) myocytes, over a range of stimulation frequencies (from 0.1 to 7.0 Hz) with reversal of electrode polarity after each stimulus to prevent the development of pH gradients around each electrode. Unlike quiescent, unstimulated myocytes, the amplitude of contraction, and velocities of shortening and relaxation did not change in myocytes paced at 3-5 Hz for up to 72 h. The maintenance of normal contractile function in paced myocytes required mechanical contraction per se, since paced myocytes that remained quiescent due to the inclusion of 2.5 microM verapamil in the culture medium for 48 h also exhibited a decline in contractility when paced after verapamil removal. Similarly, pacing increased peak calcium current compared with quiescent cells that had not been paced. Thus myocyte contraction at physiological frequencies induced by continual uniform electric field stimulation in short-term primary culture in defining medium maintains some biophysical parameters of myocyte phenotype that are similar to those observed in freshly isolated adult ventricular myocytes.

Animals↗
PubMed1993

Cognitive shifting as a predictor of progress in social understanding in high-functioning adolescents with autism: a prospective study.

Although striking and pervasive failure of social understanding is commonly viewed as a major defining characteristic of people with autism, few follow-up reports were published that have focused on improvement of social intelligence. In this prospective study in which 17 high-functioning adolescents with autism were involved, cognitive shifting as measured by card sorting tests, unlike overall intelligence, was shown to be the only significant factor in predicting progress in social understanding as assessed by social comprehension tests. A pretest-posttest design was used. During the 2-year follow-up all the subjects were in residential care and enrolled in educational curricula focusing on the development of social intelligence, living, and vocational skills.

Adolescent↗
PubMed1993

Impaired cognitive shifting in parkinsonian patients on anticholinergic therapy.

In this study we established that cognitive shifting, an ability that is known to be affected in PD, is more impaired in PD patients, treated with anticholinergics, than in de novo patients. Eleven PD patients on anticholinergic monotherapy were compared with 30 de novo patients. The groups did not differ with respect to age, duration and severity of PD, and depression, nor with respect to general intelligence or attention. We assessed cognitive shifting with three different card-sorting tests. The patients on anticholinergics showed a poorer performance on all card-sorting tests than the de novo patients did. The patients on anticholinergics needed significantly more trials in two card-sorting tests and discovered significantly less categories in total. There was also a significant difference in memory performance, but memory performance did not correlate with any score on the card-sorting tests. This indicates that the performance on card-sorting tests and the memory performance were independent.

Aged↗
PubMed1993

Short-term memory in Parkinson's disease after withdrawal of long-term anticholinergic therapy.

We assessed the short-term memory (STM) using the Visual Paired Associates and the Verbal Paired Associates test, and the motor status at the end of 7.8 +/- 3.7 years of anticholinergic therapy in 22 nondemented patients with Parkinson's disease (PD). Eighteen patients managed to stop anticholinergic therapy. During anticholinergic therapy, STM in PD is significantly worse than in normal controls (CS). Two months after the withdrawal of anticholinergic drugs, the STM retest gain is significantly greater in PD than in CS, and at that time STM in PD did equal CS levels. After withdrawal of anticholinergic therapy, thirteen patients noticed a deterioration of motor function; the dose of levodopa had to be increased in seven patients. We conclude that in nondemented PD patients, long-term anticholinergic therapy probably does not result in irreversible damage to STM, and withdrawal of long-term anticholinergic therapy is feasible in the majority of PD patients.

Aged↗
PubMed1993

Activated complement directly modifies the performance of isolated heart muscle cells from guinea pig and rat.

The complement system has been implicated in the pathogenesis of cardiovascular disorders including ischemia and atherosclerosis. Selective deposition of C5b-9, the membrane attack complex of complement, has been histochemically documented in human myocardium early after reperfusion of ischemic areas and in infarcted zones. However, functional sequelae of the C5b-9 complex binding to myocardial cells have not been identified. Insertion of C5b-9 complexes into the membrane of other cell types can generate transient changes in membrane permeability in the absence of cell lysis. We demonstrate in beating isolated adult guinea pig and rat cardiac myocytes that human derived C5b-9 can transiently augment in a dose-dependent manner both basal cytosolic calcium concentration and calcium transients, resulting in a temporary increase in contractility. If similar changes occur in human heart cells in vivo, they could significantly affect myocardial performance and contribute to functional abnormalities seen in ischemia and other pathological conditions associated with complement activation.

Animals↗
PubMed1993

Adult rat ventricular myocytes cultured in defined medium: phenotype and electromechanical function.

We studied primary short-term cultures of adult rat ventricular myocytes in defined medium to determine whether phenotype and electromechanical function are maintained in rod-shaped, quiescent cells. Although > 80% of the myocytes retained their rod-shaped in vivo morphology for up to 72 h, contractile function as measured by cell edge motion declined 30-50% from 6 to 24 h, paralleling a 68% shortening of action potential duration. From 24 to 72 h, contractility remained unchanged. Ca2+ channel current density increased 55% after 24-48 h and then returned to the level of freshly isolated cells (9 +/- 1 pA/pF, mean +/- SE). Resting membrane potential (-71 +/- 1 mV) and action potential overshoot (34 +/- 3 mV) did not change. The ratio of alpha- to beta-myosin heavy chain mRNA and the level of cardiac alpha-actin mRNA were maintained for 8 days. Thus quiescent adult rat ventricular myocytes in defined medium undergo extensive phenotypic adaptation within 72 h of isolation, despite maintenance of a rod-shaped morphology and stable levels of contractile protein mRNA, which may limit their suitability for electrophysiological and contractile function studies.

Animals↗