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Biomedical subjects

B Janssen

Publications and source records attributed to B Janssen.

At least 19 recordsLinked to original sources

[Guidelines based on decision support software. Quality management in neurological outpatient schizophrenia treatment].

The positive effect of greater adherence to evidence-based guidelines on possibilities of optimizing diagnosis and therapy has been shown various times. Electronic systems for interactive support and systematization of physicians' decision-making represent a relatively new method for implementing guidelines. Introducing the "schizophrenia module", newly developed decision support software is presented combining electronic data processing-based, quality-oriented documentation and interactive decision support in the outpatient treatment for schizophrenic disorders. Structure, functionality, and options of use are presented. Besides classic measures of quality management (benchmarking), electronic decision support systems can contribute to improve process quality and outcome in the treatment of mental diseases.

Ambulatory Care↗

MLPA analysis for the detection of deletions, duplications and complex rearrangements in the dystrophin gene: potential and pitfalls.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X-chromosomal recessive disorders caused by mutations in the dystrophin gene. Using the novel multiplex ligation-dependent probe amplification (MLPA) method we performed retrospective and prospective analyses in a total of 193 individuals. Deletions or duplications were identified in 14 out of 90 families previously tested negative by multiplex PCR or FISH analysis. Partially incorrect results were subsequently identified in two families: the loss of exon 38 signal in one case was due to a p.Q1802X nonsense mutation, whilst in another patient an apparent deletion of exon 37 (coinciding with a duplication of exons 46-53) was caused by a p.R1735C polymorphism. In one case we found a complex rearrangement involving a duplication of two regions: dupEX45-48 and dupEX54-55. We conclude that MLPA is a highly sensitive and rapid alternative to multiplex PCR. It can be used on blood samples, chorionic villi and paraffin-embedded tissue. The ease of detection of duplications and the application for female carrier analysis are clearly the main advantages of the method. However, apparent single exon deletions detected by MLPA should be checked by an independent method. Complex rearrangements such as double mutations on the same allele are rare.

DNA Primers↗

[Are bonus systems applicable to guideline-oriented depression treatment provided by general practitioners and neurologists?].

In the outpatient treatment of depression, the potential of diagnostic and therapeutic methods is seldom exhausted resulting in variable quality of treatment and partly insufficient cost effectiveness. Implementation of a guideline-oriented reimbursement system seems to be an option to improve quality of treatment. Corresponding incentive systems have been outlined and evaluated for the health care of somatic diseases such as diabetes. Acting on these experiences, an attempt was made to utilize them for the area of psychiatric disorders. Taking depression as an example, a model for a quality-oriented, guideline-based reimbursement system for general and specialist practice is presented.

Ambulatory Care↗

[Guideline conformity and outcome of inpatient treatment for schizophrenia. A clinical comparison].

Patient outcome and guideline conformity in inpatient schizophrenia treatment was systematically evaluated and compared with 597 patients across seven psychiatric hospitals. Patient structure and treatment processes showed a great variability between hospitals. Patient characteristics, especially mental state, and the chronicity of the disease were the strongest predictors of clinical outcome. Outcome evaluation using quality indicators is only possible after case-mix adjustment taking into account prognostic factors. A poorer average clinical outcome was associated with lower guideline conformity in a variety of treatment domains. After case-mix adjustment, benchmarking is an opportunity to improve quality of treatment and promote guideline conformity.

Adult↗

Guideline adherence in medication management of psychotic disorders: an observational multisite hospital study.

OBJECTIVE: To evaluate guideline adherence in in-patient medication care of psychotic disorders. METHOD: A total of 508 persons with psychotic disorders were included in a naturalistic multisite hospital study. Subjects were assessed weekly on mental state, social functioning, socioeconomic factors and medication prescriptions. RESULTS: In total, 17% of individuals were prescribed antipsychotic dosages above the recommended value. Among those with persistent psychotic symptoms, 73% received insufficient antipsychotic drug management. About 58% of patients with depressive symptoms were not treated according to guidelines, and 53% of patients did not receive adequate management of side-effects from antipsychotic medications. Subjects with more than six previous psychiatric hospitalizations (OR 1.80, CI: 1.05-3.08) and those with a prominent thought disorder (OR 2.28, CI: 1.23-4.23) had a higher likelihood of not being treated according to guidelines. CONCLUSION: Individuals with chronic and thought-disordered psychosis may be at a higher risk of receiving medication care not supported by guidelines.

Adult↗

Magnetic resonance imaging of regional cardiac function in the mouse.

In this paper we introduce an improved harmonic phase (HARP) analysis for complementary spatial modulation of magnetization (CSPAMM) tagging of the mouse left ventricular wall, which enables the determination of regional displacement fields with the same resolution as the corresponding CINE anatomical images. CINE MRI was used to measure global function, such as the ejection fraction. The method was tested on two healthy mouse hearts and two mouse hearts with a myocardial infarction, which was induced by a ligation of the left anterior descending coronary artery. We show that the regional displacement fields can be determined. The mean circumferential strain for the left ventricular wall of one of the healthy mice was -0.09 +/- 0.04 (mean +/- standard deviation), while for one of the infarcted mouse hearts strains of -0.02 +/- 0.02 and -0.10 +/- 0.03 were found in the infarcted and remote regions, respectively.

Algorithms↗

Atypical and typical neuroleptics in acute schizophrenia and related delusional disorders. Drug choice, switching and outcome under naturalistic treatment conditions.

Atypical neuroleptics have improved drug treatment in schizophrenia. However, their use varies greatly between countries and continents. Recent metaanalyses have deemphasized the range and magnitude of their superiority compared to typical neuroleptics. Aims of the present study were to contribute effectiveness data to this discussion. In 725 inpatients with ICD-10 diagnoses F20, 22-25 from four German psychiatric inpatient units acute neuroleptic treatment and outcome were analyzed under naturalistic conditions. Treatment strategies were stratified post hoc to answer the question, which proportion - and which kind - of patients are primarily given atypicals or typicals, for how long, at which rate and when the atypical/typical drugs are switched to typical/atypical drugs, and what the respective outcomes are. As the results demonstrate, atypicals were administered one time during inpatient treatment in nearly 48% of the patients, however as first choice drugs in only 15% of this population. Treatment change occurred in 28% after 5-6 weeks irrespective of the first drug choice. Outcome differences were, if at all, only modest and not systematically biased towards a single strategy. In conclusion, frequency of inpatient treatment with atypical neuroleptics corresponds to pharmaco-epidemiological data in Europe, but is still lower than in the US. Contrary to contemporary guideline recommendations atypical neuroleptics under routine inpatient treatment conditions were scarcely administered as first choice treatment, and acute clinical outcome is comparable to that under treatment with typical neuroleptics. Reasons and implications of these findings considering the methodological limitations are discussed.

Acute Disease↗

Modern treatment concepts in schizophrenia.

On the basis of available practice guidelines for schizophrenia, contemporary treatment principles for schizophrenia leading to phase- or stage-oriented, multidimensional treatment approaches are described. Additionally, based on current research programmes, future treatment developments are presented.

Acute Disease↗

[Better prognosis due to new treatment approaches. Therapy of schizophrenia in 2002].

Schizophrenia is a mental illness that is often chronic and can severely compromise day-to-day life. In Germany, some 800,000 people--that is, almost 1% of the population--will suffer from schizophrenia during the course of their lives. In almost 50% of schizophrenics treatment is virtually exclusively in the hands of their family doctors. For this reason, thorough familiarity with the diagnosis and treatment of this condition, in particular with more recent therapeutic options is essential for the family doctor. Despite the fact that the disease often remains chronic, the prognosis has been considerably improved by the introduction of new therapeutic approaches.

Antipsychotic Agents↗

Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity.

All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC(50)-value of 8.7 nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16 mg kg(-1). In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action.

Animals↗

Chronic measurement of cardiac output in conscious mice.

We describe the feasibility of chronic measurement of cardiac output (CO) in conscious mice. With the use of gas anesthesia, mice >30 g body wt were instrumented either with transit-time flow probes or electromagnetic probes placed on the ascending aorta. Ascending aortic flow values were recorded 6-16 days after surgery when probes had fully grown in. In the first set of experiments, while mice were under ketamine-xylazine anesthesia, estimates of stroke volume (SV) obtained by the transit-time technique were compared with those simultaneously obtained by echocardiography. Transit-time values of SV were similar to those obtained by echocardiography. The average difference +/- SD between the methods was 2 +/- 7 microl. In the second set of studies, transit-time values of CO were compared with those obtained by the electromagnetic flow probes. In conscious resting conditions, estimates +/- SD) of cardiac index (CI) obtained by the transit-time and electromagnetic flow probes were 484 +/- 119 and 531 +/- 103 ml x min(-1) x kg body wt(-1), respectively. Transit-time flow probes were also implanted in mice with a myocardial infarction (MI) induced by ligation of a coronary artery 3 wk before probe implantation. In these MI mice (n = 7), average (+/- SD) resting and stimulated (by volume loading) values of CO were significantly lower than in noninfarcted mice (n = 15) (resting CO 16 +/- 3 vs. 20 +/- 4 ml/min; stimulated CO 20 +/- 5 vs. 26 +/- 6 ml/min). Finally, using transfer function analysis, we found that, in resting conditions for both intact and MI mice, spontaneous variations in CO (> 0.1 Hz) were mainly due to those occurring in SV rather than in heart rate. These data indicate that CO can be measured chronically and reliably in conscious mice, also in conditions of heart failure, and that variations in preload are an important determinant of CO in this species.

Animals↗

Left ventricular hypertrabeculation in myotonic dystrophy type 1.

BACKGROUND: Left ventricular hypertrabeculation (LVHT) has not been described in myotonic dystrophy Type I (MD1) before. CASE REPORT: A 42-year-old man developed typical features of MD1 since 1992. Creatinekinase was slightly, but recurrently elevated. Needle electromyograms were myogenic and showed extensive spontaneous activity. Muscle biopsy was compatible with MDI. DNA analysis revealed a heterozygous 300 CTG-repeat expansion in the myotonic-dystrophy proteinkinase gene on chromosome 19q13.3. Cardiac history and clinical cardiologic examination were normal. On ECG, ST elevation and atrial flutter were found. The AECG was normal except for atrial flutter. Surprisingly, transthoracic echocardiography revealed LVHT, previously described only in Becker's muscular dystrophy, mitochondriopathies, and Barth syndrome. CONCLUSION: A rare cardiac manifestation of MD1 may be LVHT which alone has no therapeutic implication.

Adult↗

Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene.

BACKGROUND: Familial primary pulmonary hypertension (PPH) is an autosomal-dominant inherited disease with incomplete penetrance and poor prognosis. This study was performed to examine whether asymptomatic carriers of a mutated PPH gene can be identified at an early stage by their pulmonary artery systolic pressure (PASP) response to exercise. METHODS AND RESULTS: Stress Doppler echocardiography during supine bicycle exercise and genetic linkage analysis were performed on 52 members of 2 families with PPH. In 4 PPH patients, the mean PASP was increased at rest (73+/-16 mm Hg). Fourteen additional family members with normal PASP at rest revealed an abnormal PASP response to exercise (from 23+/-4 to 56+/-11 mm Hg) without secondary cause (abnormal response [AR] group). Twenty-seven other members (NR group) revealed a normal PASP response (maximal pressure <40 mm Hg) to exercise (from 24+/-4 to 37+/-3 mm Hg, P<0. 0001). All 14 AR but only 2 NR members shared the risk haplotype with the PPH patients. The molecular genetic analysis supported linkage to chromosome 2q31-32 with a logarithm of the odds score of 4.4 when the 4 patients and the 14 AR members were classified as affected. CONCLUSIONS: We conclude that the pathological rise of PASP in asymptomatic family members is linked to chromosome 2q31-32 and is probably an early sign of PPH. Therefore, stress Doppler echocardiography may be a useful tool to identify persons at risk for PPH even before pulmonary artery pressures at rest are elevated.

Adolescent↗

Construction of a 350-kb sequence-ready 11q13 cosmid contig encompassing the markers D11S4933 and D11S546: mapping of 11 genes and 3 tumor-associated translocation breakpoints.

Previously, we located three novel human tumor-associated translocation breakpoints in the chromosome 11q13 region between the markers D11S4933 and D11S546. To facilitate the molecular analysis of these breakpoints, we have constructed a continuous sequence-ready cosmid and PAC contig of approximately 350 kb, including the markers D11S4933 and D11S546. In addition, a detailed transcript map was generated. This resulted in the precise positioning of 11 genes and ESTs within the contig, including 4 genes already known to map in the 11q13 region. Three other genes that we positioned within the contig showed homologies to unmapped genes from human and/or other species. Three ESTs were novel. Partial cosmid sequencing resulted in the establishment of the direction of transcription of several of the reported genes. This contig will be instrumental for the detailed characterization of the tumor-associated chromosomal breakpoints and the identification of other 11q13-associated disease genes.

Animals↗