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Biomedical subjects

W Greil

Publications and source records attributed to W Greil.

At least 19 recordsLinked to original sources

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

Stimulation by bradykinin, angiotensin II, and carbachol of the accumulation of inositol phosphates in PC-12 pheochromocytoma cells: differential effects of lithium ions on inositol mono- and polyphosphates.

Rat PC-12 pheochromocytoma cells respond to stimulation with bradykinin, angiotensin II, and carbachol with an increased formation of labeled inositol phosphates after preincubation of the cells with [3H]inositol. Li+ potentiates greatly the agonist-induced increase in amount of inositol mono-, bis-, and trisphosphate but not the increase in amount of inositol tetrakisphosphate. Separation of the isomers of inositol trisphosphate shows that the lithium-induced increase in amount of inositol trisphosphate is due to potentiation evoked by lithium of the accumulation of inositol-1,3,4-trisphosphate.

Adrenal Gland Neoplasms

Evidence that thyroid growth promoting activity of immunoglobulin preparations is due to contamination with EGF.

Immunoglobulin (IG) preparations may be contaminated with growth factors. Therefore, we investigated whether the growth promoting activity in IG preparations (thyroid growth stimulating immunoglobulins = TGI) from patients with sporadic goitre may be caused by contaminating EGF (epidermal growth factor). EGF in sera as well as in indifferently prepared IG of patients with recurrent goitre (n = 23), Graves' disease (n = 19) and normals (n = 17) was determined by EGF receptor assay. Comparatively, the ability for stimulating thyroid cell growth was determined in these IG preparations (2 mg/ml). EGF in ammoniumsulphate (AS) precipitates was about 2-fold higher than serum EGF. The growth promoting activity of indifferent IG preparations correlated with the EGF content. After additional purification on protein A-sepharose, neither EGF, nor a growth promoting activity was found in these IG preparations. We therefore conclude, that the growth promoting activity of crude IG preparations may be due to a contamination with EGF.

Animals

Hypertrophy and hyperplasia during goitre growth and involution in rats--separate bioeffects of TSH and iodine.

Goitre growth was investigated in rats receiving a low iodine diet (less than 0.1 microgram iodine/g) and either 1 g/l KClO4 or 1 g/l propylthiouracil (PTU), or a combination of KClO4 or PTU with 50.82 nmol/1 T3 in tap water for 3 weeks. To investigate goitre involution, rats with iodine-deficient goitres were treated for 3 weeks either with T3 (0.5 microgram T3/day = 0.768 nmol/day), iodide (0.5 or 2.7 micrograms KI/day) or a combination of T3 with both iodide doses. Histology together with total DNA distinguished between hypertrophy and hyperplasia of the gland. During goitre growth there was highly significant correlation between goitre weight and TSH serum level (r = 0.93, P less than 0.001). Thyroid total DNA, however, was only weakly correlated to TSH but was inversely related to the degree of iodine deficiency. During goitre regression, TSH levels were normalized, histological signs of hypertrophy had disappeared, and thyroid weight was nearly normalized in all therapy groups. Total DNA, however, was normalized only with 2.7 micrograms KI/day (95 +/- 18 micrograms DNA/gland), and still elevated in all other groups. The highest DNA levels were found under T3 therapy (143 +/- 21 micrograms DNA/gland) and under 0.5 microgram KI/day (161 +/- 19 micrograms DNA/gland). Reduction of total DNA was independent of TSH, but followed replenishment of the iodine content of the glands. We conclude that TSH mainly induces hypertrophy, whereas thyroid hyperplasia is mainly regulated by the intracellular iodine content.

Animals

Inhibition of cAMP formation by EGF in thyroid follicles is mediated by intracellular Ca++.

The mechanism of cAMP-inhibition by EGF was studied in isolated porcine thyroid follicles. EGF inhibited TSH-induced cAMP-formation maximally by 40%, this effect remained up to 1 h of pre-incubation. The calcium-ionophore A 23 187 also inhibited cAMP-formation, but its effect was relieved after 1 h. The phorbolester TPA had a biphasic influence on cAMP-formation, with a transient increase (5 min) before a sustained inhibition (60 min); the inhibitory effect was mimicked by the diacylglycerol 1-oleoyl-2-acetyl-glycerol. Exogenous arachidonic acid had only a small and transient inhibitory effect on cAMP-formation. We conclude, that EGF inhibits cAMP-formation by a raise of intracellular Ca++, as well as by the direct activation of proteinkinase C, indicating, that a phosphorylated product could be a mediator for the inhibition of adenylate cyclase.

Animals

Paracrine interaction between thyrocytes and fibroblasts.

Cell free supernatants (conditioned medium) of isolated porcine thyroid follicles, stimulated with EGF (5 ng/ml) or TSH (1-1000 microU/ml), were tested for a mitogenic activity for fibroblasts. Whereas TSH-conditioned medium dose-dependently stimulated [3H]thymidine incorporation into DNA of fibroblasts, only a weak stimulation was found with EGF. However, when the changes in cell number were determined, a significant increase was only found with EGF-conditioned medium from thyroid follicles. The cause of this discrepancy is a dose-dependent stimulation of [3H]thymidine incorporation into fibroblasts by cAMP and thyroid hormones. Cyclic AMP, however, does not stimulate growth of fibroblasts. IGF I production is stimulated in fibroblasts by basal as well as EGF stimulated conditioned medium of thyroid follicles. In contrast, TSH-conditioned medium inhibited IGF I production in fibroblasts. Conditioned medium itself is free of detectable IGF I. As IGF I stimulates not only growth of fibroblasts, but also of thyrocytes, we conclude, that conditioned medium from thyrocytes stimulates IGF I production in fibroblasts, which itself stimulates fibroblast and thyrocyte growth.

Animals