Call a halt to strong-arm tactics over GM crops.
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Civil Disorders↗
Biomedical subjects
M Philipp
Publications and source records attributed to M Philipp.
[Staging of musculoskeletal tumors in diagnostic imaging].
The staging of primary malignant bone and soft tissue tumors requires adherence to a unified staging system. The staging system of the American Joint Commission for Cancer, the Enneking system, and the Hajdu system are described in respect of the radiologic staging criteria. Plain film radiography can estimate the biological aggressiveness of a bone tumor and in many cases narrow the differential diagnosis. Computed tomography is most sensitive in depicting cortical erosions and calcified periosteal reactions as well as in screening for distant metastasis. Angiography is mainly employed for vascular tumors and for the monitoring of interventional procedures such as tumor embolization. For both bone and soft tissue tumors, magnetic resonance tomography is the method of choice for the staging of intra- and extramedullary tumor extension, for the differentiation of neighboring compartments, and in the detection of invasion of the regional neurovascular bundle. After administration of contrast agents, the mode of enhancement gives further information on the nature of the tumor. With consistent application of the staging criteria in preoperative imaging, limb-saving therapy can be employed more often and the prognosis of the disease can be improved.
Bone Neoplasms↗
Angiotensinogen T174M and M235T gene polymorphisms are associated with the extent of coronary atherosclerosis.
BACKGROUND: The relations of the angiotensinogen (AGT) T174M and M235T gene polymorphisms to the risk of coronary heart disease (CHD) have been investigated in only a few studies with conflicting results. RESULTS: Therefore, we analysed the relationship of the AGT gene polymorphisms to the presence and extent of CHD in 2250 male Caucasians whose coronary anatomy was defined by means of coronary angiography. The relative frequencies of the T and M alleles of the T174M and of the M235T gene variation did not significantly differ between patients without or with single-, double- or triple-vessel disease and between subjects without or with myocardial infarction (MI). In contrast the mean CHD score--defined by Gensini--was higher within MM homozygotes of the T174M gene variation than within TT genotypes; TM subjects had intermediate values. In M235T genotypes, mean CHD scores were similar in the total sample and in older individuals (> or = 62 years), whereas in younger individuals (< 62 years) a higher CHD score was found within AGT 235 T allele carriers than within MM homozygotes. In younger individuals with high apoAI plasma levels, the mean CHD score was clearly higher within TT homozygotes of the M235T gene variation than within MM genotypes; MT subjects had intermediate values. An interaction between both angiotensinogen gene polymorphisms on the extent of CHD or on the risk of non-fatal MI were not observed when the M allele of AGT T174M was combined either with the T allele or the TT genotype of M235T. CONCLUSIONS: The present study strengthens the hypothesis of an association of both angiotensinogen gene polymorphisms with the extent of coronary heart disease.
Alleles↗
The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease.
BACKGROUND: There are conflicting results on the relationship of N5,N10-methylenetetrahydrofolate reductase C677T gene variation in coronary artery disease and myocardial infarction. METHODS AND RESULTS: We analysed this gene variation in 2453 male Caucasians whose coronary anatomy was defined by coronary angiography. In the total sample, the C677T gene polymorphism was not associated with the presence or the extent of coronary artery disease (defined by the degree of vessel disease or by the coronary heart disease score according to Gensini). However, after excluding individuals with low risk profiles, an association between the C677T TT genotype and the Gensini score was found. This observation applies only to individuals (i) with high glucose levels, (ii) with low apolipoprotein Al/apolipoprotein B ratios, (iii) with low apolipoprotein Al/apolipoprotein B ratios and high lipoprotein (a) levels and (iv) with low apolipoprotein Al/apolipoprotein B ratios and high glucose concentrations. In patients with high glucose levels, the paraoxonase 191 A/B gene variation presupposed whether differences in Gensini scores between C677T C allele carriers and TT homozygotes became apparent, since only in paraoxonase 191 AA homoxygotes, but not in paraoxonase 191 B allele carriers, did C677T TT homozygotes have clearly higher Gensini scores than C allele carriers (two-way interaction; P = 0.013). The MTHFR C677T gene polymorphism was not associated with non-fatal myocardial infarction. CONCLUSION: The present study extends previous observations by the finding that carriers of the N5,N10-methylenetetrahydrofolate reductase C677T TT genotype with various coronary high risk profiles had clearly higher coronary heart disease scores than individuals with at least one C677T C allele.
Adult↗
Undesirable blood pressure changes under naturalistic treatment with moclobemide, a reversible MAO-A inhibitor--results of the drug utilization observation studies.
Blood pressure decrease, associated with postural hypotension, as well as spontaneous hypertension are considered to be typical side-effects of conventional, irreversible and nonselective MAO (A+B) inhibitors. The new generation of reversible MAO-A inhibitors is, however, expected to have negligible cardiovascular effects and low propensity to induce either blood pressure increases or decreases. But, the true incidence of such changes is largely unknown since observation studies, specifically assessing the frequency of blood pressure changes, in unselected population of patients treated in the practice, are lacking.
Adult↗
A new promoter polymorphism in the gene of lipopolysaccharide receptor CD14 is associated with expired myocardial infarction in patients with low atherosclerotic risk profile.
Recent findings suggest that inflammation plays a role in atherosclerosis and its acute complications. Cellular response in infections with Gram-negative bacteria is mediated by bacterial lipopolysaccharide (LPS), which activates monocytes to expression of cytokines, growth factors, and procoagulatory factors via LPS receptor CD14. Endothelial cells and smooth muscle cells are stimulated by a complex of LPS and soluble CD14. In this study, LPS receptor CD14 was analyzed to find genetic variants and check them for an association with coronary artery disease or myocardial infarction (MI). When screening the CD14 gene by single-strand conformation polymorphism analysis, a promoter polymorphism was detected and confirmed as a T-to-C exchange at position -159. We determined the genotypes of 2228 men who had undergone coronary angiography for diagnostic purposes. Within the total study group there was no significant association of either genotype with MI or coronary artery disease. However, in a subgroup with low coronary risk (normotensive nonsmokers), a relative risk for MI in probands homozygous for the T allele could be evaluated (OR, 1.6; 95% CI, 1.0 to 2.4; P<0.05). The association was even stronger in low-risk patients older than 62 years (OR, 3.8; 95% CI, 1.6 to 9.0; P<0.01). In conclusion, we describe a new CD14 promoter polymorphism that is associated with MI, especially in older patients with a low atherosclerotic risk profile.
Aged↗
Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology -- a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group.
The benzamide amisulpride (ASP) is a selective D2-like dopamine antagonist, while flupentixol (FPX), a thioxanthene, blocks D2-like, D1-like and 5-HT2 receptors. To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability, a randomized double-blind multi- center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia (DSM-III-R) with predominant positive symptomatology. Doses were initially fixed (ASP: 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% in case of side effects (mean daily doses: ASP: 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement under both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI: 0.55; 10.65) in favour of ASP. According to CGI, 62% of patients in either drug group were treatment responders. ANCOVA analysis showed that reductions of BPRS (ASP: -42%; FPX: -32%) and SAPS (ASP: -78%; FPX: -65%) were more pronounced under ASP. Due to adverse events, significantly fewer ASP patients (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolerability was better in the ASP group, as demonstrated by smaller increases in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate. ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology, while extrapyramidal tolerability is better. These conclusions have to be drawn cautiously, as dosage effects on outcome parameters cannot be entirely ruled out. The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability.
Adult↗
Association of the platelet glycoprotein IIIa PlA1/A2 gene polymorphism to coronary artery disease but not to nonfatal myocardial infarction in low risk patients.
BACKGROUND: The platelet membrane glycoprotein IIb/IIIa functions as a receptor for fibrinogen and von Willebrand factor during platelet aggregation. In a small case-control study, evidence has been presented that the PlA2 allele of the platelet glycoprotein GPIIIa PlA/A2 gene polymorphism might be an independent risk factor for acute myocardial infarction (MI). METHODS AND RESULTS: We explored the association of the PlA1A2 to the severity of coronary artery disease (CAD), as assessed angiographically in 2252 male individuals, and to myocardial infarction (MI). The severity of coronary heart disease (CHD) was also estimated by calculating a CHD score according to Gensini. The PlA genotype was determined by allele specific restriction digestion. Relation of the PlA2 allele to CAD: In the total population, the frequency of the PlA2 allele was not associated to the presence or to the extent of CAD. Also the CHD scores of PlA1/PlA2 genotypes were essentially the same. However, after exclusion of individuals with high BMI (> or =26.9 kg/m2) and/or low apoAI (< 1.43 g/l) PlA2PlA2 carriers had clearly higher CHD scores than PlA1PlA1 genotypes: PlA1PlA2 heterozygotes had intermediate values (p <0.05). After division of the study population into one group of individuals without any angiographic signs of CAD (CHD score = 0) and into another group of patients with severe CAD (CHD score (> or = 120), a strong association of the PlA2 allele with severe CAD was also found in the same low risk groups: e.g. exclusion of persons with high BMI and low apoAI resulted in an Odds ratio of 5.37 (1.46-19.7) (p <0.02). Relation of the PlA2 allele to MI: No association was found between PlA1/PlA2 genotypes and risk of MI neither in the total population nor in low risk subgroups. CONCLUSIONS: Whereas no difference in the distribution of allele and genotype frequencies between controls and survivors of MI could be detected, the PlA2 allele is associated with CHD in low risk patients.
Aged↗
Response to treatment in minor and major depression: results of a double-blind comparative study with paroxetine and maprotiline.
Several concepts of minor depression in the sense of acute but less severe symptomatology than major depression have been proposed in the literature, but currently none of them is generally accepted. For the treatment of these conditions, only few recommendations based on empirical data are available. We conducted a randomized double-blind multicentre study in depressed outpatients comparing paroxetine and maprotiline in both patients with minor (n = 245) and major depression (n = 298). For the diagnosis, Research Diagnostic Criteria were used in a modified version. Two response criteria were applied: a reduction of 50% or more in total HAMD-17 scores from baseline (criterion 1), and a reduction of the HAMD-17 total score to 9 points or less (criterion 2). A completer and an endpoint analysis was performed. For patients with minor depression, remarkably high response rates were found for paroxetine (criterion 1: 90.9% completer, 82.1% endpoint; criterion 2: 89.1% completer, 82.4% endpoint) while the respective rates for maprotiline tended to be lower (criterion 1: 80.4% completer, 71.4% endpoint; criterion 2: 84.9% completer; 76.1% endpoint). Response rates in patients with major depression were for paroxetine: criterion 1: 74.3% completer, 62.8% endpoint; criterion 2: 76.4% completer, 65.2% endpoint; and for maprotiline: criterion 1:82.4% completer, 68.5% endpoint; criterion 2: 80.6% completer; 66.0% endpoint, which resembles rates reported from previous antidepressant trials. Both drugs were generally well tolerated. Though no placebo control was carried out, our results suggest that minor depression is a disorder that is very likely to respond to antidepressant pharmacotherapy with paroxetine, but also with maprotiline at a favourable risk/benefit ratio.
Adolescent↗
A double-blind study comparing paroxetine and maprotiline in depressed outpatients.
A double-blind multicenter randomized parallel group study comparing paroxetine and maprotiline was carried out in a total of 544 outpatients. Included were patients with varying degrees of severity of depressive symptoms who fulfilled modified RDC criteria for either Minor or Major Depression and showed a HAMD-17 score of > or = 13. No concomitant benzodiazepine treatment was allowed. Duration of treatment was 6 weeks, after an initial wash-out period. Doses were fixed during the first 3 weeks of treatment, patients receiving either 20 mg paroxetine or 100 mg maprotiline daily. An option for dose escalation was provided for insufficient responders after 3 weeks. The weekly assessments comprised rating of the HAMD-17, MADRS, BRMS, RDS, HAMA, CAS, and CGI scales and registration of adverse events by non-leading questions. An intention-to-treat and a completer analysis were performed. Response was defined as a HAMD-17 reduction of > or = 50% or a HAMD-17 score of < or = 9 at the end of the study or at dropout. The treatment groups were comparable according to demographic data. Overall evaluation indicated equieffective and good antidepressant and anxiety-reducing properties for paroxetine and maprotiline. No persistent significant differences between treatment groups were observed on any assessment instrument. There was no difference in the frequency of observed side-effects, but side-effect profiles were markedly different, as maprotiline patients had more anticholinergic and paroxetine patients more SSRI-typical side-effects.
Adult↗
Guidelines for the implementation of drug utilization observation (DUO) studies in psychopharmacological therapy. The "Phase IV Research" Task-Force of the Association for Neuropsychopharmacology and Pharmacopsychiatry (AGNP).
The task-force on Phase-IV-Research of the Association for Neuropharmacology and Pharmacopsychiatry (AGNP) has developed guidelines for the implementation of scientifically sound drug utilisation observation studies (DUO studies). These guidelines have been adopted by the executive committee as the position of the association. DUO studies are prospective pharmacoepidemiological studies, by which prescription, illness, and patient data of individual patients are collected without interference with the routine course of treatment. They can answer questions on the interaction of treatment modalities with positive and negative treatment outcome. Scientific standards require that there is a study protocol which describes the epidemiological, statistical, procedural, and quality assurance methodology and states who is responsible for what. As such studies can violate data protection regulations or can be used for sales instead of scientific purposes, consultation of an ethics committee is recommended.
Clinical Trials, Phase IV as Topic↗
Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective study in depressed out-patients with inadequate treatment response.
In view of the fact that controlled prospective studies on the benefits of dose escalation of the selective serotonin re-uptake inhibitor (SSRI) paroxetine are lacking, we conducted a double-blind, randomized, parallel-group multicentre study designed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria (RDC) with inadequate treatment response. The study sample consisted of 544 out-patients with different degrees of severity of depression. Patients received either 20 mg paroxetine (n = 271) or 100 mg maprotiline (n = 273) for the first 3 weeks in a double-blind manner. Response after 3 weeks was defined using explicit operationalized criteria. Patients with inadequate treatment response (paroxetine group, n = 86; maprotiline group, n = 88) were again randomized to either continuation of the previous dosage (paroxetine, n = 36; maprotiline, n = 48) or increased doses, i.e. 40 mg paroxetine (n = 50) or 150 mg maprotiline (n = 40), respectively. Intention-to-treat and completer analyses were performed. Defining response as a reduction in Hamilton Depression Rating Scale (17-item version) (HAMD-17) score of at least 50% from baseline, no significant benefits of dose escalation were found for either paroxetine or maprotiline. Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation. After dose escalation, new adverse events that had not been present during treatment with lower doses rarely occurred. Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients.
Adult↗
Hypertension with moclobemide.
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Antidepressive Agents↗
The deficit syndrome in schizophrenic and nonschizophrenic patients: preliminary studies.
One hundred and eighty-seven patients suffering from DSM-III-R schizophrenia, schizoaffective, schizophreniform (psychotic group), unipolar, bipolar and other disorders were interviewed 5 years after discharge. Deficiencies were assessed by means of the Schedule for Deficit Syndrome (SDS) and the Scale for Assessment of Negative Symptoms (SANS). Binocular thresholds for discomfort to high luminances (TDHL) were assessed in 17 patients with a deficit syndrome. Results suggest that patients with psychotic disorders are in a high-risk group for deficit syndrome. Nevertheless, 9-28% and 9-30% of the 'nonpsychotic' group according to the SANS and the SDS, respectively, showed primary enduring negative symptoms. A positive correlation between the SANS total score and TDHL (r = 0.81) was found. These results suggest the nonspecificity of primary enduring negative syndromes. Furthermore preliminary data indicate a possible link between light sensitivity and the deficit syndrome, independently of diagnoses.
Chronobiology Phenomena↗
[Pharmacotherapy of anxiety disorders].
Many out-patients suffer from anxiety disorders which can be diagnosed and treated pharmacologically by the family doctor. In a study of our own, including 500 outpatients with actual complaints being not sufficiently explainable by physical findings, we could diagnose anxiety disorders according to DMS-III-R in 21% of the cases (9). Knowing the basic diagnostic rules, which differentiate between the different types of anxiety disorders, a differential and rational treatment with benzodiazepines, antidepressants and neuroleptics is possible. Knowing the typical risks, applying the correct rules of indication, and accepting the counselling of a psychiatrist when necessary, the family doctor will be able to undertake a qualified primary pharmacological treatment of anxiety disorders.
Anti-Anxiety Agents↗
Subtypes of negative symptoms: the primary subtype in schizophrenic and non-schizophrenic patients.
1. The specificity of negative symptoms remains an open question and requires further research. 2. Subtyping negative symptoms has been showed to be a very relevant point for the identification of primary negative symptoms and for their pharmacotherapy. Negative symptoms as a whole have been demonstrated in schizophrenic and non-schizophrenic patients, but these studies did not report about the primary and secondary subtypes. 3. The present study is the first one investigating primary negative symptoms in schizophrenic and non-schizophrenic patients. 84 consecutively admitted psychiatric patients have been studied 5 years after their discharge. 4. All negative symptoms (including the primary subtype) according to Carpenter (Kirkpatrick et al. 1989) and Andreasen (Andreasen 1981) could be identified in all diagnostic groups.
Female↗
[Modification of sexual functions by antidepressants].
Sexual dysfunctions appear to be frequently occurring adverse events in treatment with antidepressants. Due to methodological reasons, a reliable estimation of the frequency of such events is currently not yet possible. There is evidence, that antidepressants could be differentiated with respect to their potency and specificity for disturbances of certain sexual subfunctions according to their pharmacological profile. With SSRIs in particular impaired functions of orgasm and ejaculation can be observed. No deteriorations are reported for buproprion and an improvement of sexual dysfunctions within the course of treatment for moclobemide. Viloxazine and trazodone appear to possess marked stimulating effects on libido and erectile functions. Generally the incidence of sexual adverse events is underestimated, although there is a pronounced impact on patient compliance. Taking into account this well documented side effect, sexual impairments should be monitored carefully within antidepressive treatment.
Antidepressive Agents↗
[Minor depression--how useful and valid a diagnostic concept].
Recent classification research has shown, that there is a great number of mildly depressed patients, who do not fit into the more severe diagnostic criteria of major depression. We therefore asked whether it is necessary to introduce a diagnostic category of minor depression below that of major depression. Using a large outpatient sample, we studied whether such a diagnosis of minor depression would reach sufficient validity according to a variety of independent validation criteria. The results were not very convincing. We therefore discuss alternative definitions of mild depression.
Depression↗