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Biomedical subjects

P Jørgensen

Publications and source records attributed to P Jørgensen.

At least 19 recordsLinked to original sources
PubMed2005

Integrated treatment ameliorates negative symptoms in first episode psychosis--results from the Danish OPUS trial.

PURPOSE: To investigate the effect of integrated treatment on negative, psychotic and disorganised symptoms in patients with first episode psychosis. METHOD: A RCT comparing integrated treatment (IT) with standard treatment (ST) was conducted, including 547 patients, aged 18-45, diagnosed with schizophrenia spectrum disorders. All patients were assessed with SCAN, SAPS and SANS at entry and after 1 and 2 years. The IT consisted of assertive community treatment, multifamily groups, psycho-education and social skills training, and the caseload was 1:10 compared with 1:25 in ST. Since attrition was considerable, a mixed model analysis with repeated measurements was used to examine the possible effects of IT statistically. RESULTS: IT reduced both negative and positive symptoms significantly better than ST. Most marked were the results from the negative dimension, where all five global scores from SANS had a significantly better reduction in IT. Sub-analyses did not single out any one element in the integrated treatment that could explain this result. CONCLUSION: Integrated treatment significantly reduced both negative and psychotic symptoms, assumably due to the different psychosocial treatment elements that were provided in the IT. The results indicate that the integrated approach is crucial, since, most likely, many aspects of the integrated treatment have contributed to the reduction of symptoms.

Adolescent↗
PubMed2002

Presence of clone-specific markers at birth in children with acute lymphoblastic leukaemia.

Recent studies have suggested that development of childhood acute lymphoblastic leukaemia may often be initiated in utero. To provide further evidence of an prenatal origin of childhood leukaemia, we conducted a molecular biological investigation of nine children with B-precursor acute lymphoblastic leukaemia carrying the chromosomal translocation t(12;21), the most common subtype of all childhood acute lymphoblastic leukaemia. Specifically, for each child we identified the non-constitutive chromosomal sequences made up by the t(12;21) fusion gene. From these, leukaemia clone-specific DNA primers were constructed and applied in nested polymerase chain reaction analyses of DNA extracted from the patients' Guthrie cards obtained at birth. Leukaemia clone-specific fusion gene regions were demonstrated in Guthrie card DNA of three patients, age 2 years 11 months, 3 years 4 months, and 5 years 8 months at leukaemia diagnosis. Our findings are consistent with previous observations, and thus provide further evidence that the development of t(12;21) B-precursor acute lymphoblastic leukaemia may be initiated in utero. Review of the current literature moreover indicates that age at leukaemia may be inversely correlated with the burden of cells with leukaemia clonal markers, i.e. leukaemia predisposed cells at birth, and that certain types of childhood acute lymphoblastic leukaemia develop as a multiple step process involving both pre- and postnatal genetic events.

Adolescent↗
PubMed2002

Anaerobic power and muscle strength characteristics of 11 years old elite and non-elite boys and girls from gymnastics, team handball, tennis and swimming.

The aim of the present investigation was to study the possible effects of specificity of training on muscle strength and anaerobic power in children from different sports and at different performance levels in relation to growth and maturation status. Hundred and eighty-four children of both gender participating either in swimming, tennis, team handball or gymnastics were recruited from the best clubs in Denmark. Within each sport, the coach had divided the children into an elite (E) and non-elite (NE) group according to performance level and talent. Tanner stage assessment and body weight and height measurements were performed by a physician. The anaerobic performances were assessed by Wingate tests and jumping performance in squat jump (SJ), countermovement jump (CMJ) and drop jump (DJ) from two heights. Most of the differences between groups in Wingate performance disappeared when the data were normalised to body mass. The gymnasts were the best jumpers and their superiority were increased in the more complex motor coordination tasks like DJ. The results may indicate some influence of training specificity, especially on the more complex motor tasks as DJ and there may be an effect of training before puberty. The performance in the less complex motor tasks like cycling and SJ and CMJ may also be influenced by specific training, but not to the same extent, and heritance may be an important factor for performance in these anaerobic tasks.

Anaerobic Threshold↗
PubMed2002

OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with first-episode psychosis. One-year follow-up of a randomised controlled trial.

BACKGROUND: Patients with first-episode psychosis comprise a high-risk group in terms of suicide. AIMS: To identify predictive factors for suicidal behaviour and to examine the effect of integrated treatment on suicidal behaviour and hopelessness. METHOD: A total of 341 patients with a first-episode schizophrenia-spectrum disorder were randomised to integrated treatment or treatment as usual. RESULTS: During the 1-year follow-up period, 11% attempted suicide. This was associated with female gender, hopelessness, hallucinations and suicide attempt reported at baseline, with the two latter variables being the only significant ones in the final multivariate model. The integrated treatment reduced hopelessness. CONCLUSIONS: Hallucinations and suicide attempt before inclusion in the study were the most significant predictors of suicide attempt in the follow-up period.

Adolescent↗
PubMed2000

Interaction between the transcription factor SPBP and the positive cofactor RNF4. An interplay between protein binding zinc fingers.

The activator of stromelysin 1 gene transcription, SPBP, interacts with the RING finger protein RNF4. Both proteins are ubiquitously expressed and localized in the nucleus. RNF4 facilitates accumulation of specific SPBP-DNA complexes in vitro and acts as a positive cofactor in SPBP-mediated transactivation. SPBP harbors an internal zinc finger of the PHD/LAP type. This domain can form intra-chain protein-protein contacts in SPBP resulting in negative modulation of SPBP-RNF4 interaction.

3T3 Cells↗
PubMed2000

Early detection and assertive community treatment of young psychotics: the Opus Study Rationale and design of the trial.

BACKGROUND: Recent research indicates that early detection of young persons suffering from psychosis and subsequent intensive intervention enhances treatment response and prognosis, but the data are only preliminary and suggestive. METHOD: We present the rationale and design of the largest study to date to evaluate two major issues in the field of secondary prevention: (1) Does education and intensified collaboration with general practice, social services etc. reduce the duration of untreated psychosis? and (2) Can modified assertive community treatment improve the course and outcome in young persons suffering from psychosis as compared to treatment in community mental health centres? The article aims additionally to put the study in context and assist in designing future studies. RESULTS: Preliminary experiences are described. The findings of the first 312 patients show that modified assertive community treatment results in patients adhering to treatment significantly better than standard treatment in community mental health centres. CONCLUSION: The surge of interest in preventively oriented detection and treatment models for untreated psychosis in young people calls for research programmes and evidence. The obstacles to this are manifold. The initial findings of the OPUS study suggest, however, that better adherence to treatment is possible.

Adolescent↗
PubMed1999

Decreased glutamate metabolism in cultured astrocytes in the presence of thiopental.

The effect of thiopental on glutamate metabolism was studied by 13C magnetic resonance spectroscopy. Cerebral cortical astrocytes were incubated with 0.5 mM [U-13C]glutamate for 2 hr in the presence of 0.5 or 1 mM thiopental. Labeled glutamate, glutamine, aspartate, and glutathione were observed in cell extracts, and glutamine, aspartate, and lactate in the medium. Not only present in the medium was uniformly labeled glutamate, but also glutamate derived from the tricarboxylic acid (TCA) cycle, and thus glutamate release could be detected. The amounts of [U-13C]glutamate and unlabeled glucose taken up by astrocytes were unchanged in the presence of 0.5 mM thiopental and decreased to about 50% and 80%, respectively when the concentration was increased to 1 mM. The amounts of most metabolites synthesized from [U-13C]glutamate were unchanged in the presence of 0.5 mM thiopental, but decreased [U-13C]glutamine, [U-13C]aspartate, and [U-13C]lactate were observed in the 1 mM group. Surprisingly, the amounts of [1,2,3-13C]glutamate, [2,3-13C]aspartate, and [3,4-13C]aspartate (2nd turn via the TCA cycle) were unchanged. However, this was not the case for [1,2-13C]lactate and [2,3-13C]lactate. Such variations indicate cellular compartmentation, possibly caused by a heterogeneous glutamate concentration within the cells affecting TCA cycle turnover rates differently.

Anesthetics, Intravenous↗
PubMed1999

A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease.

Mutation in the presenilin-1 (PS-1) gene at chromosome 14q24.3 is the most common cause of autosomal dominant early-onset Alzheimer's disease. Here, we report a novel missense mutation in the presenilin-1 gene found in a three-generation Danish family with autopsy-verified early-onset Alzheimer's disease. Two affected first-degree relatives in two generations were found to be heterozygous for a cytosine to adenine transversion at the second position of codon 116, which changes the amino acid at that position from threonine to asparagine. This conservative amino acid substitution occurs in an evolutionary highly conserved region of the PS-1 protein and is associated with onset of the disease between age 35 and 41 years and 4-8 years' duration of the disease. Analysis of amyloid beta-protein (A beta) deposition in brain specimens from one affected family member showed predominance of A beta 42(43). Onset and progression of the disease were very similar in two sibs homozygous for the epsilon 3 allele and the epsilon 4 allele, respectively, of the polymorphic apolipoprotein E locus. The lack of effect of the high risk epsilon 4/epsilon 4 genotype on the disease in this family corroborates and extends previous observations that the presence of one copy of the epsilon 4 allele does not modulate PS-1 associated Alzheimer's disease.

Adult↗
PubMed1998

Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia.

We have developed a multiplex reverse transcription-polymerase chain reaction (RT-PCR) reaction, which enables us to detect 29 translocations/chromosomal aberrations in patients with acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Through the construction and optimization of specific primers for each translocation, we have been able to reduce the set-up to 8 parallel multiplex PCR reactions, thus greatly decreasing the amount of work and reagents. We show the value of our set-up in a retrospective analysis on cryopreserved material from 102 AML and 62 ALL patients. The multiplex RT-PCR detected a hybrid mRNA resulting from a structural chromosomal aberration in 45 of 102 (44%) of the AML and in 28 of 62 (45%) of the pediatric ALL cases. Importantly, in 33% of AML and in 47% of the ALL cases with cytogenetic data, submicroscopic chromosomal aberrations or masked translocations were shown that were not detected in the cytogenetic analysis either for structural reasons or because of an insufficient number of metaphases obtained. This multiplex RT-PCR system, which can handle up to 10 patients with a response time of 2 working days, is thus an important tool that complements cytogenetic analysis in the up-front screening of acute leukemia patients and should provide a rapid and efficient characterization of leukemia cells, even in situations with sparse patient material.

Acute Disease↗
PubMed1998

Schizophrenic delusions: the detection of warning signals.

Schizophrenic delusions are important target symptoms for treatment. This study aims to identify predictors of delusion formation. Two samples of schizophrenic patients (total n = 131) are examined prospectively every second week during a period of 6 months. In one sample (n = 60) delusion formation (n = 27; 45%) is correlated significantly with a change in score of eight individual items from the Early Signs Scale (ESS): sleep, anxiety, concentration, irritability, coping, tiredness, depression and confusion. These eight items form the Warning Signals Scale (WSS). The predictive validity of the scale is tested in another sample (n = 71), of which 43 patients (61%) have reemergence of delusions. A criterion cut-off score of > or = 5 points combines an acceptable sensitivity (77%) and specificity (68%). The scale is acceptable to patients, manageable for clinicians, and it has a high degree of predictive validity and reliability. This makes it relevant for implementation in ordinary clinical practice.

Adult↗
PubMed1998

Early signs of psychotic relapse in schizophrenia.

BACKGROUND: People with schizophrenia are at high risk of psychotic relapse. The purpose of this study was to evaluate the predictive validity and temporal link of early signs to this. METHODS: A study sample of 60 out-patients with schizophrenia was examined every second week over a period of six months. The study design included self-reporting (Early Signs Scale) and objective assessment (General Psychopathology of Positive and Negative Symptom Scale) of behavioural and phenomenological changes (early signs). Criterion cut-off points were based on a comparison to the subjects' individual baseline scores. RESULTS: Twenty-seven subjects (45%) experienced a relapse. Composite increased score (> or = 10 points) of self-reported/objectively assessed early signs predicted the relapse with a sensitivity of 81% and a specificity of 79%. Thus the predictive validity of early signs of relapse was considerable, particularly self-reporting of early signs of relapse: sensitivity 74% and specificity 79%. The inclusion of objective assessment added only marginally to the prediction. Early signs were detected most often (70%) within the four weeks immediately before the individuals' relapse. CONCLUSION: Psychotic relapse is most often preceded by early signs. Clinical practice should integrate this knowledge by an ongoing monitoring including self-reporting.

Adult↗
PubMed1997

A novel MLL-AF10 fusion mRNA variant in a patient with acute myeloid leukemia detected by a new asymmetric reverse transcription PCR method.

A novel variant of the chimerical MLL-AF10 mRNA transcript was detected in a pediatric patient with acute myeloid leukemia (AML) by a new asymmetric reverse-transcription polymerase chain reaction (ART-PCR) method. Sequence analysis of the fusion region on the amplified cDNA fragment showed an in-frame joining of exon e5 of the MLL gene and position 1931 of the cDNA sequence of the AF10 gene, giving rise to a new MLL-AF10 transcript. The presence of the new chimerical mRNA product in a sample from the patient was confirmed by classical RT-PCR.

Acute Disease↗
PubMed1997

Acute and transient psychotic disorder: a 1-year follow-up study.

A study sample consisting of 51 patients suffering from acute and transient psychotic disorder (ATPD) (ICD-10) on initial examination was evaluated at 1-year follow-up. The findings show a diagnostic change in half of the patients (48%), most often to schizophrenia (15%) and affective disorder (28%). From index admission to follow-up, patients with an unchanged diagnosis of ATPD manage fairly well with regard to psychosocial functioning, and no deteriorating development is observed. In the majority of cases no personality disorder (PD) (ICD-10, 54%; DSM-IV, 71%) is apparent, and the ATPD is not related to any specific PD. With regard to diagnostic stability, no significant demographic, social or clinical predictors were found. The findings highlight the need for validation of the concept of ATPD, and point to the fact that brief psychotic episodes with an acute onset may be an early manifestation of severe mental disorder (schizophrenia and affective disorder).

Acute Disease↗
PubMed1997

Complementation of a primer binding site-impaired murine leukemia virus-derived retroviral vector by a genetically engineered tRNA-like primer.

Reverse transcription of retroviral genomes is primed by a tRNA annealed to an 18-nucleotide primer binding site. Here, we present a primer complementation system to study molecular interaction of the replication machinery with the primer and primer binding site in vivo. Introduction of eight base substitutions into the primer binding site of a murine leukemia virus-based vector allowed efficient RNA encapsidation but resulted in severely reduced vector replication capacity. Replication was restored upon complementation with a synthetic gene designed to encode a complementary tRNA-like primer, but not with a noncomplementary tRNA-like molecule. The engineered primer was shown to be involved in both the initiation of first-strand synthesis and second-strand transfer. These results provide an in vivo demonstration that the retroviral replication machinery may recognize sequence complementarity rather than actual primer binding site and 3' primer sequences. Use of mutated primer binding site vectors replicating via engineered primers may add additional control features to retroviral gene transfer technology.

Animals↗