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Biomedical subjects

A Wägner

Publications and source records attributed to A Wägner.

At least 19 recordsLinked to original sources
PubMed2002

Differences in resting state regional cerebral blood flow assessed with 99mTc-HMPAO SPECT and brain atlas matching between depressed patients with and without tinnitus.

An increased occurrence of major depressive disorder has been reported in tinnitus patients, and of tinnitus in depressive patients. Involvement of several Brodmann areas (BAs) has been reported in tinnitus perception. The aim of this study was to assess the regional cerebral blood flow (rCBF) changes in depressed patients with and without tinnitus. The rCBF distribution at rest was compared among 45 patients with a lifetime prevalence of major depressive disorder, of whom 27 had severe tinnitus, and 26 normal healthy subjects. 99mTc-hexamethylenepropylene amine oxime (99mTc-HMPAO) single photon emission computed tomography (SPECT), using a three-headed gamma camera, was performed and the uptake in 34 functional sub-volumes of the brain bilaterally was assessed by a computerized brain atlas. Decreased rCBF in right frontal lobe BA 45 (P<0.05), the left parietal lobe BA 39 (P<0.00) and the left visual association cortex BA 18 (P<0.05) was found in tinnitus patients compared with non-tinnitus patients. The proportion of tinnitus patients with pronounced rCBF alterations in one or more of the temporal lobe BAs 41+21+22 was increased compared to gender matched controls (P<0.00) and patients without tinnitus (P<0.05). Positive correlations were found between trait anxiety scales from the Karolinska Scales of Personality and rCBF in tinnitus patients only in three limbic BAs (P<0.01), and inverse correlations in non-tinnitus patients only in five BAs subserving auditory perception and processing (P<0.05). rCBF differences between healthy controls and depressed patients with and without tinnitus were found in this study. The rCBF alterations were distributed in the cortex and were particularly specific in the auditory cortex. These findings suggest that taking audiological symptoms into account may yield more consistent results between rCBF studies of depression.

Age Factors↗
PubMed2000

Registration of neuroimaging data: implementation and clinical applications.

Image registration brings images into a form in which each voxel corresponds to a predetermined anatomic entity and is necessary for comparisons of data across scans. Intrasubject registration is a matter of translating and rotating one image volume into correspondence with another. Intersubject registration is more difficult because it requires the removal of individual anatomy dependence from the data. This article describes, with the help of clinical examples, automated methods for intrasubject registration of scans within and between modalities, and intersubject registration used for registering a three-dimensional brain atlas with a patient's brain scan.

Adult↗
PubMed1999

Cost-effectiveness and accuracy of the tests used in the differential diagnosis of Cushing's syndrome.

AIM: Establish the minimal biochemical and radiological examinations necessary and their cost-effectiveness to accurately diagnose the etiology of Cushing's syndrome (CS). MATERIAL AND METHODS: In 71 patients with CS followed between 1982 and 1997 biochemical studies (basal ACTH, 8 mg dexamethasone suppression test-HDST-, metyrapone stimulation test-MST-, or inferior petrosal sinus catheterization-IPSC-) and radiological investigations (abdominal CT scan, pituitary CT scan or MRI) were performed. Once pathology confirmed the diagnosis (48 pituitary Cushing's disease-CD, 17 adrenal neoplasms, 2 bilateral macronodular hyperplasia-BMH-, and 4 ectopic ACTH syndrome-ES-), the sensitivity, specificity, positive and negative predictive value of the different studies was calculated to establish the most accurate and cost-effective diagnostic protocol. RESULTS: In ACTH-independent CS (ACTH < or = 9 pg/ml; normal 9 to 54) a unilateral tumor was identified on abdominal CT scanning in 17, and BMH in 1; the other BMH had detectable ACTH (43.2 pg/ml). In ACTH-dependent CS, ACTH was > 9 pg/ml and IPSC (performed in 22) correctly identified 20 patients with CD and differentiated them from 2 with an ES (100% specificity and sensitivity). Pituitary MRI or CT did not disclose an adenoma in 41.7% of patients with CD, and was reported to exhibit a microadenoma in 2 of the 4 patients with ES. HDST and MST were of no additional use in the differentiation between CD and ES. CONCLUSIONS: Once CS is diagnosed low ACTH and an abdominal CT scan correctly identified all patients of adrenal origin. In ACTH-dependent CS IPSC was the best predictive test to differentiate CD from ES. BMH may behave as ACTH-dependent or independent. The other biochemical and radiological studies performed are not cost-effective and may even be misleading, and should not be routinely performed.

ACTH Syndrome, Ectopic↗
PubMed1999

Prolonged inhibition of glutamate reuptake down-regulates NMDA receptor functions in cultured cerebellar granule cells.

In the present study, we have examined the effects of prolonged (up to 72 h) inhibition of high-affinity glutamate reuptake by L-trans-pyrrolidine-2,4-dicarboxylate (PDC; 100 microM) on glutamate receptor functions in primary cultures of rat cerebellar granule neurons. This was done by comparing the effects of various glutamate receptor agonists on neuronal 45Ca2+ uptake, free cytoplasmic Ca2+ concentration ([Ca2+]i), and cell viability. We also determined the parameters of[3H]MK-801 binding as well as the expression of the NMDAR1 subunit protein in control and PDC-exposed cultures. The blockade of glutamate reuptake by PDC led to a gradual increase of ambient glutamate to concentrations that are neurotoxic when applied acutely to control cells. In PDC-exposed cells, however, the acute glutamate-induced NMDA receptor-mediated calcium fluxes were strongly diminished and no toxicity was observed. The down-regulation of the functional effects of glutamate was dependent on the duration of PDC exposure and was accompanied by a reduced NMDAR1 subunit expression and decreased [3H]MK-801 binding, indicative of a pronounced structural rearrangement of NMDA receptors. The possibility that the decrease of NMDA glutamate receptor sensitivity can be explained on the basis of a reduced density or altered subunit composition of NMDA receptors is discussed.

Animals↗
PubMed1999

Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas.

Surgery is the treatment of choice for many pituitary tumors; pituitary function may suffer after operation, but relief of pressure on the normal pituitary may also favor postoperative recovery of hypopituitarism. The aim of this study was to investigate the frequency of new appearance and recovery of hypopituitarism after neurosurgery and try to identify features associated with it. Pre- and postoperative anterior pituitary functions were investigated in 234 patients with pituitary adenomas (56 nonfunctioning, 71 PRL-secreting, 66 GH-secreting, 39 ACTH-secreting, 1 LH/FSH-secreting, and 1 TSH-secreting tumors). Eighty-eight new postoperative pituitary hypofunctions appeared in 52 patients (12 NF, 14 PRL-secreting, 15 GH-secreting, 10 ACTH-secreting, and 1 LH/FSH-secreting adenomas). They corresponded to 27% ACTH deficiencies (in 29 of the 107 patients with normal preoperative ACTH in whom postoperative evaluation was complete), 14.5% (15 of 103) new GH deficiencies, 10.5% (15 of 143; P < 0.0005, significantly less than ACTH deficiency) new TSH deficiencies, 16.5% (20 of 121) new gonadotropin deficiencies, and 13% (9 of 71) new PRL deficiencies. Preoperatively, 93 were deficient in at least 1 pituitary hormone; after surgery, 45 (48%) recovered between 1 and 3 hormones. The 2 patients with LH/FSH- and TSH-secreting macroadenomas did not recover pituitary function. Factors associated with a higher probability of postoperative pituitary function recovery were: no tumor rests on postoperative pituitary imaging (P = 0.001) and no neurosurgical (P = 0.001) or pathological evidence (P = 0.049) of an invasive nature. Tumor size did not differ significantly between those who did and those who did not recover pituitary function after surgery. Even if clear hypofunction is observed at initial work-up, patients should be reassessed after surgery without substitution therapy, because practically half the preoperative pituitary hormone deficiencies recover postoperatively, eliminating the need for life-long substitution therapy.

Adenoma↗
PubMed1991

Effects of clomipramine treatment on cerebrospinal fluid monoamine metabolites and platelet 3H-imipramine binding and serotonin uptake and concentration in major depressive disorder.

In an open study of 12 inpatients who met the DSM-III criteria for a major depressive episode, the effects of clomipramine (CI) on the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured simultaneously with the effects on 3H-imipramine binding, serotonin (5-HT) uptake and 5-HT concentration in platelets after 3 and 6 weeks of treatment. Drug (CI and desmethylclomipramine) plasma concentrations were determined. The concentrations of 5-HIAA and HMPG decreased substantially, and the concentration of HVA remained unchanged. There was also a large and significant reduction of the number of imipramine binding sites (Bmax) and of the platelet 5-HT concentration. The 5-HT uptake was not measurable after 3 weeks of treatment. None of the parameters changed significantly between weeks 3 and 6. There were no significant correlations between antidepressant effect (measured by the Montgomery-Asberg Depression Rating Scale) and plasma drug concentrations, although a tendency to a significant correlation between antidepressant effect and CI was observed at 3 weeks. There were no significant intercorrelations between the different 5-HT parameters and no other significant correlations between the biochemical measures and clinical outcome.

Adult↗
PubMed1989

Circadian variation of platelet 3H-imipramine binding, platelet serotonin content, and plasma cortisol in healthy volunteers.

Platelet 3H-imipramine binding, platelet serotonin content, and plasma cortisol were measured in 10 healthy female volunteers. Samples were taken on 5 occasions with a 6-hr interval during a 24-hr period within 1 week in May. Although there were individual variations in the biochemical parameters over a 24-hr period, we could not establish a clear common circadian rhythm for all subjects in platelet 3H-imipramine binding and platelet serotonin concentrations. During the night, there was a significant decrease in Bmax values and a slight, but not significant, increase in serotonin concentrations. A distinct circadian rhythm was obtained for plasma cortisol, with lowest values during the night.

Adult↗
PubMed1987

Effects of antidepressant treatments on platelet tritiated imipramine binding in major depressive disorder.

The effects of four antidepressant treatments on platelet tritiated imipramine binding have been studied in 51 hospitalized patients with severe major depressive disorder. There was an increase in maximum binding (Bmax) during the first week of treatment with antidepressants and electroconvulsive therapy, which was further magnified after three weeks' treatment with the serotonin uptake blockers alaproclate and zimeldine hydrochloride, but the Bmax values returned to baseline levels with nortriptyline hydrochloride and electroconvulsive therapy. The equilibrium dissociation affinity constant (Kd) did not change with any of the treatments. On reexamination one or two years after admission to the study, Bmax had not reached control values in clinically recovered, drug-free patients. Low pretreatment Bmax was associated with delusions during illness and with a poor long-term clinical outcome. There was no correlation between binding parameters and monoamine metabolite concentrations in the cerebrospinal fluid, either before or during treatment.

Adult↗
PubMed1986

Biochemical effects of antidepressant treatment--studies of monoamine metabolites in cerebrospinal fluid and platelet [3H]imipramine binding.

Two putative markers of serotonergic function, the concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the binding parameters of [3H]imipramine to blood platelets, are discussed. Pretreatment concentrations of 5-HIAA in the cerebrospinal fluid (CSF) are lower in depressed patients than in normal controls, and a low concentration of the metabolite is associated with an increased risk of suicide. Many studies have attempted to use pretreatment concentrations of 5-HIAA, of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and of the dopamine metabolite homovanillic acid (HVA) as predictors of therapeutic effect. On the whole, HVA appears to predict the effects of diverse treatments rather better than 5-HIAA. Treatment with antidepressant drugs changes the amine metabolite concentrations in the CSF in a relatively predictable way. Thus, administration of selective inhibitors of serotonin uptake has a more profound effect on CSF 5-HIAA, while noradrenaline uptake inhibitors preferentially reduce CSF MHPG concentrations. The Bmax of [3H]imipramine binding to blood platelets has been found to be lower in untreated depressed patients than in healthy controls in several studies. In a study from our group, three weeks' treatment with the serotonin uptake blockers zimeldine and alaproclate increased Bmax, while neither nortriptyline nor electroconvulsive treatment caused any change in Bmax after this time period. One year after initiation of treatment, patients who had clinically recovered and were no longer taking drugs still had a low Bmax of [3H]imipramine platelet binding. Prophylactic lithium caused a significant, but transient decrease in the Bmax of platelet [3H]imipramine binding in euthymic bipolar patients.

Antidepressive Agents↗
PubMed1986

Therapeutic effects of serotonin uptake inhibitors in depression.

Depression has been associated with a disturbance in serotonin function as reflected in platelet uptake of the transmitter as well as in CSF levels of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA). CSF 5-HIAA levels are subnormal in approximately 30% of melancholia patients. Early studies suggested that patients with a disturbed serotonin metabolism were less responsive to treatment with uptake inhibitors with a preferential action on noradrenaline neurons. Such findings encouraged the search for compounds with a selective effect on serotonin neurons. Although some classical antidepressants are potent inhibitors of serotonin uptake, they are not selective, since their metabolites, which appear to have antidepressant effects, inhibit noradrenaline uptake. The consistent findings of an increased risk for suicide in patients with low CSF 5-HIAA underlines the importance of exploring drugs that act on serotonin transmission. The biochemical effects of some serotonin uptake inhibitors and their clinical and research potential in depression are reviewed.

5-Hydroxytryptophan↗
PubMed1986

Solid state conformations and antidopaminergic effects of remoxipride hydrochloride and a closely related salicylamide, FLA 797, in relation to dopamine receptor models.

The X-ray structures of two new 2,6-disubstituted benzamides, i.e., remoxipride hydrochloride monohydrate [-)-(S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenza mide hydrochloride monohydrate) and FLA 797 [-)-(S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamide ), have been determined as well as the distribution coefficients. The difference in dopamine receptor blocking activity is discussed in terms of lipophilicity and solid state conformations of the two benzamides. The major difference between the solid state conformations lies in the orientation of the carboxamide moiety. In remoxipride the carbonyl group is oriented almost perpendicularly to the benzene ring, thus preventing the formation of a hydrogen-bonded pseudo-ring between the amide hydrogen and the methoxy group found in other types of o-methoxybenzamides. In FLA 797, however, this pseudo-ring is present in the planar conformation of the salicylamide moiety. This conformation is further stabilized by a hydrogen bond between the phenol group and the carbonyl oxygen. The side chain in remoxipride adopts an extended conformation in contrast to FLA 797, where the side chain has a folded conformation. The crystal structures are related to current topographic dopamine receptor models developed from more rigid antidopaminergic compounds. Based on these comparisons, it is suggested that benzamides having an N-ethyl-2-pyrrolidinylmethyl side chain interact with the receptor in the folded conformation. The binding affinity is thought to be further increased by the planar conformation of the salicylamide moiety present in FLA 797, which permits an efficient pi-pi stacking interaction.

Benzamides↗
PubMed1985

Lower 3H-imipramine binding in platelets from untreated depressed patients compared to healthy controls.

3H-Imipramine binding in platelets was measured in 63 severely depressed hospitalized patients, who had been drug free (with the exception of moderate doses of benzodiazepines) for at least 1 month, and in 53 healthy control subjects of comparable age and sex distribution. Bmax of 3H-imipramine binding was significantly lower in the depressed subjects (1012 +/- SD 295 vs. 1123 +/- SD 178 fmole/mg protein). Depressed patients who had attempted suicide by violent means tended to have higher Bmax than nonviolent attempters.

Adult↗
PubMed1984

Weak binding of 10-hydroxymetabolites of nortriptyline to rat brain muscarinic acetylcholine receptors.

The relative affinities of nortriptyline (NT) and its 10-hydroxymetabolites to rat brain muscarinic acetylcholine receptors have been determined by competition with 3H-quinuclidinyl benzilate binding. It is shown that the major NT metabolite, E-10-OH-NT, has only 1/18 the affinity of NT for the muscarinic receptor. Since this metabolite is equipotent to NT in inhibiting neuronal noradrenaline uptake, it is suggested that it might be of clinical value as an antidepressant by virtue of having less anticholinergic side-effects than NT itself.

Amitriptyline↗