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Biomedical subjects

W Greil

Publications and source records attributed to W Greil.

At least 37 records · Page 2Linked to original sources

Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Data from a randomized prospective trial.

Recent findings have indicated that lithium treatment markedly reduces suicide risk in major affective disorders. To compare the effect of lithium with carbamazepine and amitriptyline, suicidal behavior was analyzed during the randomized prospective long-term MAP study (N = 378; duration 2.5 years). Of the nine suicides and five attempted suicides, none took place during lithium treatment. The findings support the view that lithium has a specific antisuicidal effect over and above its prophylactic benefit.

Adolescent↗

[Mefloquine-induced psychoses--problems in etiologic classification based on 2 case reports].

Psychiatric disorders following treatment with Mefloquine were described several times since the introduction of this antimalarial drug in Germany in 1985. On the basis of two case reports problems of the diagnosis and of the correlation of psychiatric disorders with the medication are discussed. Particularly are an analysis of the development of the ADR and a comparison of the psychiatric symptoms with known ADR-cases and with other psychiatric diseases important. This seems to be significant for an optimal treatment as well as for the assessment of the prognosis.

Adolescent↗

[The role of hereditary, clinical and pharmacokinetic factors in predicting the prophylactic effect of lithium salts].

In the framework of a multicentre WHO research program results of prophylactic treatment with lithium carbonate of 77 patients with affective phasic disorders were compared with a series of clinical parameters, specificity of lithium pharmacokinetics and the background characteristics of families in the groups of responders (68.8%) and non-responders. Correlations of efficacy with pharmacokinetic parameters were absent. Better preventive effect of lithium salts took place in male patients with disharmonic features of premorbid personality if their disease and prophylactic treatment started in young or in the middle age, if the disease was diagnosed as bipolar form of manic-depressive psychosis and attained its cyclothymic level with a periodical type of the prior phases. A significant accumulation of affective psychoses was found in the families of the responders. Possibility of prognostic significance of all the analyzed indices is discussed.

Adolescent↗

The recruitment process for a multicenter study on the long-term prophylactic treatment of affective disorders.

The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders. Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons. Further, a number of patients equal to that eventually allocated to the trial refused to participate for personal, idiosyncratic reasons. In spite of this, the patients in the trial were very similar to those not participating with respect to relevant variables such as age, sex, number of and intervals between previous episodes or severity of the present episode.

Adult↗

No short-term changes of cognitive performance and mood after single doses of two different lithium retard preparations.

This double-blind crossover study investigated the effects of single doses of lithium carbonate (36.6 mval), lithium-sulfate (36 mval), and placebo within the first six hours after administration. The subjects were nine healthy volunteers. The target variables were physical complaints, mood, memory, visuomotor speed, and time estimation. Subjects showed no significant impairment of performance in the cognitive tests and no subjective changes of well-being under lithium. Therefore, it seems that lithium-induced alterations of memory and mood reported in the literature develop very slowly and do not appear after a single dose.

Adult↗

Isolation and partial molecular characterization of basic fibroblast growth factor from isolated porcine thyroid follicles and entire porcine thyroid glands.

Immunoreactive basic fibroblast growth factor (bFGF) could be isolated from the cytosol preparation of isolated porcine thyroid follicles as well as in the conditioned medium from thyroid follicles in suspension culture. A double band with 16,500 and 15,500 D was detected on sodium dodecyl sulfate polyacrylamide gel electrophoresis. In dot blot and western blot the isolated peptide was immunoreactive with a specific anti-bovine bFGF antibody. For further biochemical characterization, bFGF was isolated from entire porcine thyroid glands by ammonium sulfate precipitation, cation exchange chromatography and heparin affinity chromatography. The material obtained from all three origins was identical concerning affinity to heparin and immunoreactivity with the specific anti-bovine bFGF antibody and induced neovascularization in the chorioallantois membranes of chick embryos. Amino acid sequence analysis of the 16-amino-terminal amino acids of the isolated bFGF was in accordance with the established complete 146-amino-acid bFGF molecule except that glycine in position 10 is replaced by phenylalanine. An additionally identified minor peptide presumably is an amino-terminal-truncated form of bFGF, missing the first 15 amino acids. We conclude that the physiological significance of bFGF released by thyroid cells may be the regulation of angiogenesis during thyroid development and goiter growth.

Allantois↗

Lithium determination in outpatient clinics by an ion-selective electrode in venous and capillary whole blood.

The use of an ion-selective electrode (ISE) to determine lithium (Li) in routine clinical application was evaluated by repeatedly analyzing reference specimens (precision evaluation) and by comparing blood concentrations in Li-treated patients assessed by ISE and flame emission spectrometry (FES) (correlation and agreement). Precision evaluation was sufficiently high. Li values determined by ISE in venous and capillary whole blood showed high correlations with FES plasma values (correlation coefficients between 0.86 and 0.99). Within the therapeutic range (0.3-1.0 mmole/l Li), agreement was sufficient for venous and less satisfactory for capillary blood (mean differences, FES minus ISE: -0.03 and -0.11 mmole/l Li). Above the therapeutic range, ISE values markedly exceeded FES results.

Bipolar Disorder↗

Carbamazepine-induced systemic lupus erythematosus.

A 21-year-old woman suffering from bipolar affective disorder developed systemic lupus erythematosus (SLE) with characteristic laboratory findings, 18 months after starting carbamazepine maintenance treatment. SLE receded after withdrawal of carbamazepine and treatment with anti-inflammatory drugs. Although both the spontaneous occurrence of SLE and the psychosis as a sign of CNS involvement of SLE cannot be excluded, SLE could be considered as an adverse effect of carbamazepine.

Adult↗

The agonist-stimulated accumulation of inositol phosphates is attenuated in neutrophils from male patients under chronic lithium therapy.

Neutrophils from 22 patients (11 men, 11 women) under chronic lithium therapy and from 22 age- and sex-matched healthy controls were assessed for the activity of the agonist-stimulated inositol-phospholipid second messenger-producing system. [3H]inositol-labeled cells were stimulated with the chemotactic peptide formylmethionylleucylphenyl-alanin (fMLP). The fMLP-evoked increase in the accumulation of [3H]inositol phosphates was significantly attenuated in neutrophils from chronically lithium-treated male but not female patients. Furthermore, the fMLP-stimulated accumulation of inositol phosphates was attenuated in neutrophils from male volunteers, when the labeling of the cells with [3H]inositol was performed in the presence of 1mM Li (4 hr, 37 degrees C). However, the presence of lithium ions during the labeling did not further reduce the already diminished response of neutrophils from patients under lithium therapy. These results suggest that lithium treatment induces an inhibition of the agonist-evoked breakdown of inositol phospholipids in human cells, as already shown for rat brain slices.

Adult↗

Carbamazepine distinguishes between adenosine receptors that mediate different second messenger responses.

The mechanism of the therapeutic and prophylactic effects of carbamazepine (CBZ) in affective psychoses is unknown but may in part be related to the potent competitive interaction of CBZ with adenosine-binding sites in the brain. The anticonvulsant and sedative properties of CBZ are reminiscent of the effects evoked by adenosine-agonists and contrast sharply with the opposite actions of adenosine-antagonists like caffeine. However, indirect evidence suggests an antagonist- rather than an agonist-like activity of CBZ at adenosine-receptors. We have used various model systems, in which adenosine receptor subtypes mediate different second messenger-responses, to investigate this-apparent paradox. CBZ was found to antagonize the A1-receptor-mediated inhibition of cyclic AMP accumulation in cultured astroblasts and in GH3-cells. Furthermore, CBZ also inhibits the adenosine-induced increase in the level of cyclic AMP in cultured astroblasts, which is mediated by low-affinity A2b-receptors. In contrast, CBZ does not block the inhibition elicited by adenosine-agonists of the agonist-induced increased formation of inositolphosphates in human neutrophils, which is mediated by high-affinity A2a-receptors. The specific antagonism by CBZ of A1- but not of high-affinity A2a-receptors was further supported by binding experiments using rat brain membranes. These results suggest that the paradox of CBZ's antagonistic effects at adenosine-receptors might be at least partially reconciled by a selective antagonistic action of CBZ at A1 receptors but not at high-affinity A2a-receptors.

Adenosine↗

Assessment of compliance-related attitudes in psychiatry. A comparison of two questionnaires based on the Health Belief Model.

In a study of 118 psychiatric patients two questionnaires of similar content that are supposed to predict compliance with pharmacotherapy in psychiatry were examined, "COSS" and "KK-Skala". These questionnaires assess the patient's attitudes towards his illness, pharmacotherapy, and the physician. Patient compliance was judged by the treating physicians. The results of discriminant analyses indicated that about two thirds of the patients were correctly classified into "compliant" and "moderately or not compliant" (as judged by the physicians) by means of COSS and KK-Skala, respectively. It is a matter for further research whether these results reflect in fact moderate associations between patient attitudes and compliant behavior or are due to limitations of the questionnaires and of the study design.

Adult↗

Growth regulation of porcine thyroid follicles in-vitro by growth factors.

Primarily intact thyroid follicles were isolated from explanted thyroid glands of hogs immediately after sacrifice. These intact thyroid follicles had a preserved polarity, still contained thyroglobulin, could be liberated from contaminating mesenchymal single cells and could be kept in culture for at least 14 days. They respond to bovine TSH (1 mU/ml) with a 10-fold increase in cAMP production within 15 min, trapp and organify iodine and secrete thyroid hormones. In contrast to thyroid monolayers, prepared from these thyroid follicles, intact thyroid follicles did not proliferate in response to bTSH (1-1000 uU/ml) stimulation. When thyroid follicles, however, were stimulated with EGF (1-5 ng/ml) a dose dependent increase in cell number as well as [3H]-thymidine incorporation into acid precipitable DNA was seen. The growth response of thyroid follicles to EGF (5 ng/ml) in comparison to thyroid monolayer cells was 275% versus 145% increase in cell number within 6 days. With IGF I, a proliferative response of thyroid follicles was found, and this was synergistic with simultaneous incubation with EGF. When thyroid follicles were incubated with EGF together with TSH, a dose dependent inhibition of [3H]-thymidine incorporation as well as cell number with increasing amounts of TSH (1-1000 mU/ml) occurred. The comparable effect was found, when thyroid follicles were stimulated to growth with IGF I (100 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Release of an endothelial cell growth factor from cultured porcine thyroid follicles.

It has been proposed from in vivo studies that thyroid angiogenesis during thyroid enlargement may be due to paracrine mitogenic factors released by epithelial thyroid cells. To study this paracrine growth regulating communication between thyroid cells and endothelial cells in vitro, culture medium from isolated porcine thyroid follicles was investigated for a growth promoting effect on porcine aortal endothelial cells. Serum-free conditioned medium (CM) from thyroid follicles in suspension culture contains a dose-related mitogenic activity which stimulates endothelial cell growth up to 197%. Stimulation of the thyroid follicles with TSH (1 mU/ml) significantly reduced the mitogenic activity for endothelial cells in CM to 131%. Thyroid hormones had no influence on mitogenic activity in CM. When follicles were treated with iodide (20 microM) during CM production, no proliferation of endothelial cells was observed by this CM. In contrast, CM from epidermal growth factor-treated thyroid follicles significantly enhanced the mitogenic activity for endothelial cells up to 235%. The mitogenic activity was precipitable by saturated ammonium sulfate, showed high affinity to heparin by chromatography on heparin-sepharose, and was abolished after treatment of CM with trypsin. On gel electrophoresis the heparin-binding fraction showed a double band with a mol wt of 15 and 15.5 k. These data show a paracrine mitogenic activity on endothelial cells released by thyroid follicles which is regulated by TSH, epidermal growth factor, and iodide in parallel with the direct effect of these substances on thyroid cell growth. The data suggest that the mitogenic factor is a polypeptide, which belongs to the heparin-binding growth factors.

Animals↗

Sequence of affective polarity and lithium response: preliminary report on Munich sample.

As an alternative to the bipolar I/II distinction, a subtyping of bipolar affective disorders according to the sequence of polarity (mania or depression) has been proposed. In a study of 93 patients with bipolar affective and bipolar schizoaffective disorders we tested the stability of a subtyping using the sequence of polarity. Furthermore we investigated its relationship to bipolar I/II subtypes and to response to stabilizing therapy with lithium. In the individual patient the first sequence of polarity significantly predicted the same sequence of polarity of further manifestations. However, only half of the patients could be classified as either MDI (mania-depression-interval) or DMI (depression-mania-interval). Subtyping according to the sequence of polarity was not significantly related to the bipolar I/II subgroups. MDI patients showed a significantly better response to stabilizing therapy with lithium than DMI patients. Our findings lend support to the notion that the polarity sequence is of clinical relevance. The observed association between polarity sequence and effectiveness of lithium prophylaxis could be linked to direct consequences of a MDI or DMI sequence (e.g.: different treatment approaches). On the other hand, a difference in polarity sequence might be the clinical expression of a difference in the underlying mechanisms of dysregulation, which in turn might be more or less prone to respond to lithium therapy.

Bipolar Disorder↗

RBC-choline: a biological marker of the outcome of lithium prophylaxis?

We explored whether the elevation of RBC-choline and choline ratio (RBC-choline/plasma-choline) by lithium is a specific effect of lithium, whether these choline parameters are characteristics of the individual patient, and whether they are related to prophylactic lithium response. In lithium-treated patients RBC-choline and choline ratio were highly elevated compared with untreated controls. In contrast, both values were slightly decreased in patients on antidepressants, and essentially unchanged in patients on neuroleptics. Repeated measurements showed that choline parameters were fairly stable in the individual patient. The interindividual variance was significantly greater than the intraindividual variance. In 58 affective disorder patients with established lithium response, high choline ratios were found to be associated with a poor outcome of stabilizing therapy with lithium. This finding was replicated in a new sample of 15 bipolar patients. If confirmed, it could be an important clue as to the mode of action of lithium.

Alcoholism↗