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Biomedical subjects

J Pantel

Publications and source records attributed to J Pantel.

At least 19 recordsLinked to original sources
PubMed2006

[Communication training for family caregivers of dementia patients].

The program Kommunikations-TAnDem was developed with the primary purpose of increasing the communication competence of family caregivers of dementia patients. Further aims were to reduce the burden of family caregivers and to increase the quality of life of dementia patients. The effectiveness of the Kommunikations-TAnDem was tested in a controlled training study with 22 participants using a waiting-group control design and process measurement. The results of the study verify effects for the variables "Communication competence", "Caregivers knowledge about communication in dementia", "Quality of life of dementia patients" and "Directly perceived burden of family caregivers. Therefore it can be concluded that the Kommunikations-TAnDem is a method of indirectly supporting dementia patients by training the family caregivers. The results of research in this program underline very clearly the relevance of the inclusion of the family caregivers in intervention programs and the importance of communication competence for the well-being of dementia patients and their caregivers.

Caregivers↗
PubMed2006

Temporal horn index and volume of medial temporal lobe atrophy using a new semiautomated method for rapid and precise assessment.

BACKGROUND AND PURPOSE: Quantitative markers of Alzheimer disease (AD), particularly in the early stages, are needed for clinical assessment and monitoring. We have evaluated a novel method to segment and visualize the ventricular system and obtain volumetric measures thereof. The temporal horn volume (THV) and index in patients with mild cognitive impairment (MCI) and in those with AD were evaluated. METHODS: High-resolution T1-weighted volume imaging was performed in 52 subjects (21 patients with MCI, 10 with AD, and 21 healthy control subjects). An interactive watershed transformation and semiautomated histogram analysis were implemented to produce segmented THV and temporal horn indices (THI) (ratio of THV to lateral ventricular volume). RESULTS: Cerebral ventricular and temporal horn size could be semiautomatically quantified from all 52 datasets. The method was fast and rater-independent. Qualitative ventricular inspections using surface rendering shading could uncover atrophic process with enlargement of the whole and especially temporal horn volume. Both THV and THI of patients with AD were significantly larger than those of patients with MCI or control subjects (P < .005). There was no significant difference in THV and THI between patients with MCI or control subjects (P > .05). There was a significant correlation between the neuropsychologic performance and both THI and THV across groups (P < .01). CONCLUSION: THV and THI could be used as markers of AD in the clinical environment and are expected to be helpful in monitoring therapeutic intervention.

Aged↗
PubMed2005

[Unusual course of alpha-mannosidosis with symptoms of paranoid-hallucinatory psychosis].

We report the case of a 27-year-old female with recurrent paranoid-hallucinatory episodes who was initially diagnosed as suffering from schizophrenic psychosis. After 10 years of treatment under this diagnosis, alpha-mannosidosis was identified to be the underlying cause of her psychiatric symptoms. alpha-Mannosidosis is a rare autosomal recessive lysosomal storage disorder associated with decreased activity of the enzyme mannosidase. In the present case, diagnosis was made late in the illness after failure of a response to antipsychotic treatment and with the patient additionally showing progressive cognitive decline. Only after extensive investigation was the diagnosis made by showing decreased alpha-mannosidase enzyme activity in serum and blood leukocytes. This case demonstrates that an unusual clinical course or striking symptom patterns, especially in association with somatic comorbidity, in psychotic patients should lead to diagnostic consideration of inherited metabolic disease.

Adult↗
PubMed2005

[Mild cognitive impairment and Alzheimer's disease: an investigation of the CERAD-NP test battery].

To investigate the psychometric properties of the German version of the CERAD-NP, neuropsychological deficits were compared between 49 patients with mild cognitive impairment (MCI), 80 patients with Alzheimer's disease (AD), 36 with major depression (MD), and 26 elderly controls. All participants were outpatients of the memory clinic of the Section of Geriatric Psychiatry, Heidelberg University. Diagnoses were established based on clinical examination, laboratory testing, neuroimaging, and routine neuropsychological testing according to the criteria of aging-associated cognitive decline (AACD) for MCI, NINCDS-ADRDA for AD, and DSM-IV for MD, respectively. All CERAD-NP subtests discriminated between controls and AD patients with the latter showing significantly (p< or = 0.05) lower test scores. The subtests verbal fluency and constructive apraxia differed significantly between mildly and moderately AD, while the subtests assessing declarative (epsisodic) memory performance showed only minor, non-significant differences between the respective groups. The LKB patients took an intermediate position between controls and AD patients with significantly lower scores in verbal fluency and declarative memory performance than the controls. When compared with the AD patients, MCI patients were significantly impaired in all subtests except constructive apraxia. Relative to the controls, the patients with MD showed a decreased episodic memory performance but no evidence suggesting an impairment in other neuropsychological domains. Our results indicate that the CERAD-NP is a psychometric instrument which allows a sensitive discrimination between mild and moderate AD, MCI, MD and healthy controls. However, sensitivity of discrimination between different stages of dementia varies with respect to the different subtest. While the subtest for episodic memory showed floor effects already for mild dementia, subtests for verbal fluency and constructive apraxia were able to discriminate even between more advanced stages of the disease.

Aged↗
PubMed2005

Psychiatric symptoms in alpha-mannosidosis.

Alpha-mannosidosis is characterized by mild to moderate intellectual disability (ID), moderate to severe neurosensory hearing loss, frequent infections, psychomotor disturbances and skeletal dysmorphism. For the first time, a panel of nine alpha-mannosidosis patients with psychiatric symptoms is presented. The clinical picture has several similarities: a physical or psychological stressor precedes a rapid development of a state of confusion, delusions, hallucinations, anxiety and often depression leading to a severe loss of function. This usually lasts 3-12 weeks, and is followed by a period of somnolence and asthenia. It may be more prevalent in females. In four of the described patients search for organic causes of the syndrome was performed, but revealed only negative findings. Because of the limited number of cases no firm conclusion about the benefit of various psychotropic drugs can be drawn from our observation. Psychiatric symptoms could affect as many as 25% of patients with alpha-mannosidosis. First onset is typically in late puberty to early adolescence. The episodes may be recurrent, and of limited duration although medication may be necessary to alleviate symptoms. Our observations indicate that alpha-mannosidosis is associated with an increased risk of psychiatric symptoms. These should not be dismissed as part of the ID but should give rise to the initiation of adequate diagnostic work-up, treatment and support.

Adolescent↗
PubMed2004

[Neuropsychological correlates of cerebral atrophy in Alzheimer's dementia].

This study aims to systematically analyze the relationship between neuropsychological deficits and regional cerebral atrophic changes in Alzheimer's dementia (AD). As an extension of previous studies we not only investigated substructures of the medial temporal lobe but also included other relevant cerebral regions such as frontal, temporal, and parietal lobes. This approach was based on the assumption that morphological correlates of global and specific cognitive dysfunction might reflect to a certain degree the neuronal basis of the respective function. Accordingly, the functional role assigned to a certain cerebral structure or region can be further elucidated which might lead to a better understanding of the clinical and neuropsychological heterogeneity of AD. Fifty patients with AD (NINCDS-ADRDA criteria) and 20 healthy elderly control subjects were included. All patients and controls were examined on a standardized neuropsychological test battery. In addition, magnetic resonance imaging (MRI) of the brain was performed. Volumes of the whole brain, CSF-spaces, amygdala-hippocampus complex, frontal lobes, temporal lobes, and parietal lobes were measured using a standardized protocol. AD-patients were characterized by neuropsychological deficits with respect to memory, language, praxia, cognitive speed as well as attention and concentration. These deficits were differentially correlated with regional atrophic changes. In particular, volumes of the right amygdala-hippocampus complex were correlated with declarative memory performance in the non-verbal visual domain. Furthermore, an association between left temporo-parietal regions and aspects of semantic memory, as well as verbal recall and left frontal regions could be established. The validity of our results is supported by recent findings from neuropathological and functional neuroimaging studies. In conclusion, our data indicate that MRI-based volumetry can be successfully used to detect morphological correlates of neuropsychological heterogeneity in AD and that this methodological approach allows to fruitfully study the neuronal basis of cognitive functions.

Aged↗
PubMed2003

[Magnetic resonance imaging in clinical diagnosis of dementia].

Dementing disorders belong to the most frequent neuropsychiatric diseases of the elderly population with prevalence rates of 5% in the 75 year old, but more than 10% in subjects older than 80 years. It is broadly accepted that the dementias are not caused by a single etiological factor but are attributed to a variety of different disease processes that affect the brain either directly or indirectly. According to pathoanatomic studies, two thirds of all dementias are caused by Alzheimer's disease (AD). Early recognition and differential diagnosis, which represent an important prerequisite for an optimized therapy, can be facilitated considerably by neuroimaging as well as by molecular biological findings. Therapeutic approaches include general medical management, psychosocial interventions as well as pharmacotherapy of cognitive and non-cognitive deficits. In general, early intervention using a combination of different therapeutic measures is recommended. In future, structural and functional neuroimaging might not only be used for diagnostic purposes but also to objectify and monitor the effect of treatment on relevant brain structures

Age Factors↗
PubMed2003

Corpus callosum in first-episode patients with schizophrenia--a magnetic resonance imaging study.

BACKGROUND: Morphometric studies on the corpus callosum (CC) in schizophrenia have yielded contradictory results. The aim of the present study was to investigate magnetic resonance imaging (MRI) abnormalities of the CC in first-episode patients with schizophrenic psychoses. METHOD: We assessed volumetric MRI in 31 patients with diagnoses of schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV) and a maximum exposure to neuroleptics of 2 weeks. As a control group, 12 healthy age- and sex-matched individuals were included in the study. A whole body scanner at 1.5 Tesla was used to obtain 3D T1- and T2-weighted MR datasets. The data were evaluated semi-automatically (intracranial volume, total brain volume) and manually (CC) with the software NMRwin. RESULTS: Patients had smaller CC and CC subdivisions than controls. Schizophrenic and unaffected women exhibited larger total CC and rostral subdivisions than men in both groups. Handedness did not exert an influence. CONCLUSIONS: Our findings are in line with other in vivo morphometric studies on the CC in schizophrenia. The larger CC area in women may reflect general gender-related differences in CC size as described in healthy individuals.

Adult↗
PubMed2002

[Structural cerebral changes in subjects with mild cognitive impairment].

The aim of the present study was to investigate the morphological changes in subjects with mild cognitive impairment (MCI) revealed by quantitative magnetic resonance imaging (MRI). Twenty-one subjects with cognitive impairment and 22 healthy controls were compared with 12 patients suffering from mild Alzheimer's disease (AD). The volumes of the following brain structures were assessed: total intracranial compartment, cerebrospinal fluid compartment, whole brain, and medial temporal substructures (hippocampus and parahippocampal gyrus). Subjects with mild cognitive impairment showed a significantly reduced volume of the right parahippocampal gyrus over healthy controls. Volumes of the other regions and structures did not differ between the MCI group and controls. The volumetric and neuropsychological findings of the present study support the hypothesis that mild cognitive impairment - at least in some of the affected individuals - can be seen as a preclinical stage of AD and that atrophy of the parahippocampal gyrus might be useful as an early marker of AD.

Aged↗
PubMed2001

Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4.

Studies of genetically engineered flies and mice have revealed the role that orthologs of the human LIM homeobox LHX4 have in the control of motor-neuron-identity assignment and in pituitary development. Remarkably, these mouse strains, which bear a targeted modification of Lhx4 in the heterozygous state, are asymptomatic, whereas homozygous animals die shortly after birth. Nevertheless, we have isolated the human LHX4 gene, as well as the corresponding cDNA sequence, to test whether it could be involved in developmental defects of the human pituitary region. LHX4, which encodes a protein 99% identical to its murine counterpart, consists of six coding exons and spans >45 kb of the q25 region of chromosome 1. We report a family with an LHX4 germline splice-site mutation that results in a disease phenotype characterized by short stature and by pituitary and hindbrain (i.e., cerebellar) defects in combination with abnormalities of the sella turcica of the central skull base. This intronic mutation, which segregates in a dominant and fully penetrant manner over three generations, abolishes normal LHX4 splicing and activates two exonic cryptic splice sites, thereby predicting two different proteins deleted in their homeodomain sequence. These findings, which elucidate the molecular basis of a complex Mendelian disorder, reveal the fundamental pleiotropic role played by a single factor that tightly coordinates brain development and skull shaping during head morphogenesis.

Alternative Splicing↗
PubMed2001

Reduced cerebrospinal fluid estradiol levels are associated with increased beta-amyloid levels in female patients with Alzheimer's disease.

Recent in-vitro studies indicate that estrogens such as 17beta-estradiol (E2) may decrease the production of beta-amyloid 1-42 (Abeta42), a peptide central for the formation of senile plaques in Alzheimer's disease (AD). To test this hypothesis in a clinical study, cerebrospinal fluid levels of E2 were compared between 30 female AD patients and 11 female patients with non-dementing diseases such as major depression and investigated with respect to beta-amyloid 1-40 and Abeta42 levels. E2 levels were significantly (P<0.05) lower in the AD group than in controls; within the AD group E2 levels were inversely correlated with Abeta42 concentrations (r=-0.36, P=0.05). This is the first clinical study providing evidence for an influence of E2 on Abeta42 metabolism in vivo. This observation corresponds to the putative beneficial effects of estrogen replacement therapy on the development and course of AD.

Aged↗
PubMed2001

[Quantitative magnetic resonance tomography in diagnosis of Alzheimer dementia].

Alzheimer's disease (AD) is a degenerative dementing disorder which is characterised by a progressive atrophy of several brain regions. This process may be visualised in vivo by the use of magnetic resonance imaging (MRI) in combination with appropriate volumetric post-processing techniques. Recent volumetric MRI studies in AD consistently found an extensive volume loss of the medial temporal lobe structures including amygdala and hippocampus which appeared already in the early clinical stages of the disorder. This finding is progressive during the clinical course of AD and is associated with other biological markers of the disease such as cerebrospinal fluid beta A 4 levels and apolipoprotein E genotype. With respect to the extent and the distribution of the structural changes, AD may be differentiated from other neuropsychiatric disorders which could facilitate the differential diagnosis in vivo.

Aged↗
PubMed2001

Frontotemporal dementia: clinical, neuroimaging, and molecular biological findings in 6 patients.

Establishing the diagnosis in patients with clinical signs and symptoms suggesting primary degenerative disease with marked frontal lobe involvement is difficult. Neuroimaging methods, in particular positron emission tomography (PET) with the tracer 18fluoro-2-deoxyglucose (FDG) and cerebrospinal fluid (CSF) examination of beta-amyloid and tau-protein levels may give additional information. We report five patients with clinical and radiological features of degenerative dementia with predominantly frontal involvement and one patient with primary progressive aphasia Diagnostic work-up included computed tomography (CT), magnetic resonance imaging (MRI), PET and tau-protein and beta-amyloid level determination in CSF. While neuropsychological performance varied among patients, CT and MRI demonstrated persistently frontal lobe involvement. PET revealed corresponding changes with frontal hypometabolism, but in addition, four patients (among them two with no corresponding temporal changes in CT or MRI) showed a decreased glucose uptake in the temporal cortices. CSF samples from five patients revealed elevated beta-amyloid 1-42 and tau levels in three and two patients, respectively. Reduced beta-amyloid 1-40 was found in two patients. We conclude that occurrence of clinical symptoms of frontotemporal dementia is accompanied by frontal hypometabolism regardless of additional clinical findings. The value of determination of beta-amyloid and tau protein levels remains to be determined.

Aged↗
PubMed2000

Alternative splicing at the MEFV locus involved in familial Mediterranean fever regulates translocation of the marenostrin/pyrin protein to the nucleus.

Mutations in MEFV, a gene encoding a protein (marenostrin/pyrin) of unknown function, are associated with familial Mediterranean fever, a genetic condition characterized by febrile episodes of serosal inflammation. Based on its primary structure, this 781 residue protein is thought to function as a nuclear effector molecule. However, recent transient expression studies indicated a perinuclear cytoplasmic localization. Here, we describe the isolation and expression of a novel human MEFV isoform, MEFV-d2, generated by in-frame alternative splicing of exon 2. This transcript, expressed in leukocytes, predicts a 570 residue protein designated marenostrin-d2. To investigate differences in subcellular localization between the full-length protein (marenostrin-fl) and marenostrin-d2, while providing against the overexpression of transiently expressed proteins, we have generated CHO cell lines stably expressing these two isoforms fused to the green fluorescent protein. The localization pattern of marenostrin-d2 differs dramatically from that of marenostrin-fl. Marenostrin-fl is homogeneously distributed over the entire cytoplasm, whereas marenostrin-d2 concentrates into the nucleus. To map the critical domain(s) specifying these differences, deletion mutants have been generated. Deletion of the putative nuclear localization signals (NLS) does not alter the nuclear localization of marenostrin-d2 whereas, despite the lack of discernible NLS in the domain encoded by the exon 1-exon 3 splice junction, deletion of this domain indeed disrupts this localization. These data, which challenge the current domain organization model of marenostrin, strongly suggest that MEFV encodes a nuclear protein and raises the possibility that MEFV alternative splicing may control functions of wild-type and mutant marenostrin proteins by regulating their translocation to the nucleus.

Alternative Splicing↗
PubMed2000

G-CSF plasma levels in clozapine-induced neutropenia.

BACKGROUND: Clinical reports emphasize the therapeutic usefulness of granulocyte colony-stimulating factor (G-CSF) in clozapine-induced granulocytopenia. Only sparse information exists, however, on the natural course of endogenous G-CSF plasma levels in this condition. METHODS: We monitored G-CSF and white blood cell (WBC) counts in a 73-year-old patient who developed granulocytopenia while being treated with clozapine for schizoaffective disorder. Clozapine treatment was discontinued immediately, and G-CSF serum levels were determined repeatedly during the clinical course. RESULTS: Whereas WBC counts increased again within 6 days after discontinuation of clozapine, G-CSF level decreased significantly within the same period. The rapid decrease of endogenous G-CSF levels paralleled by a normalization of neutrophil count was interpreted as the result of an intact regulatory mechanism of granulocytopoesis. Therefore G-CSF therapy was not initiated. Owing to lack of therapeutic alternatives, it was decided to reintroduce clozapine. G-CSF levels decreased further, accompanied by an increase of WBCs, indicating stable bone marrow functioning. CONCLUSIONS: Based on this observation, we assume that the course of G-CSF and WBC counts indicated an abortive form of toxic bone marrow damage with subsequent recovery. We conclude that monitoring of G-CSF levels may serve as a useful tool in the follow-up of patients in whom clozapine-induced bone marrow damage is suspected.

Aged↗
PubMed2000

Species-specific alternative splice mimicry at the growth hormone receptor locus revealed by the lineage of retroelements during primate evolution.

In humans, growth hormone receptor (GHR) transcripts exist in two isoforms differing by the retention (GHRfl) or exclusion (GHRd3) of exon 3, whereas in mice GHRfl is solely expressed. This species-specific expression pattern is believed to result from an alternative splice event that, on the basis of conflicting data obtained in humans, has been considered to be tissue-, developmentally, and/or individual-specific. To decipher the molecular basis of this unusual trait, we isolated a 6.8-kilobase fragment spanning exon 3 from individuals expressing GHRfl. Sequence analysis revealed the existence of two 99% identical retroelements flanking this exon. Unexpectedly, individuals expressing GHRd3 displayed a 2.7-kilobase deletion involving exon 3, which most likely results from an ancestral homologous recombination between the two retroelements. The lineage of these retroelements during primate evolution revealed the species specificity of the GHRd3 allele. These findings led us to propose a model underlying the existence of the sole GHRfl allele in most species. Such a retrovirus-mediated alternative splice mimicry, which clears up several as yet unexplained phenomena (i.e. the above-mentioned expression data, the Mendelian inheritance of GHR expression patterns, and the deletion of nonconsecutive exons in growth hormone resistant patients), represents a novel physiological mechanism accounting for protein diversity between and within species.

Alternative Splicing↗