Herbert Feistel

Effects of sleep deprivation on the limbic system and the frontal lobes in affective disorders: A study with Tc-99m-HMPAO SPECT

We studied 10 patients with melancholia before and after sleep deprivation and 8 controls with Tc-99m-hexamethylpropylenamineoxime (HMPAO) single photon emission computed tomography (SPECT). All depressed subjects showed relative hypoperfusion in the left anterolateral prefrontal cortex under both conditions. Only responders showed relative hyperperfusion in parts of the limbic system and a reduction of blood flow in these regions after sleep deprivation.

Dopamine and depression — Striatal dopamine D2 receptor SPECT before and after antidepressant therapy

Ten unmedicated and ten medicated patients with major depression and ten controls were investigated with IBZM-SPECT. The ten unmedicated patients were reinvestigated after treatment with tricyclic antidepressants. Dopamine D2 receptor occupancy was not different between patients and controls, or medicated and unmedicated patients. IBZM binding was increased in four patients with psychomotor retardation. Antidepressant therapy led to a decrease in IBZM binding in the five improved patients. Dopamine D2 receptor binding remained unchanged in nonresponders. It is concluded that striatal dopamine D2 receptor binding is not changed in depression or by tricyclic antidepressants; however, it is affected by psychomotor activity. The changes observed might be the result of increased tonic dopamine release in the basal ganglia, but several other explanations exist.

Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation : preliminary results

The antidepressant properties of total sleep deprivation (TSD) have been well established. There is some evidence that TSD may improve depression by altering central dopamine (DA) function. We therefore studied five depressed TSD responders and five TSD nonresponders after sleep and after TSD and five controls after sleep with IBZM single photon emission computerized tomography (SPECT). Responders showed a significant decrease (Wilcoxon--test p < 0.05) of relative basal ganglia D2 receptor occupancy after TSD compared to nonresponders (change score responders versus nonresponders p < 0.05, U-test). The data are interpreted as a sign of an enhanced DA release in responders. The results confirm previous hypotheses of dopaminergic involvement in the therapeutic action of TSD and indirectly support a dopamine hypotheses of depression.

Increased limbic blood flow and total sleep deprivation in major depression with melancholia.

Single photon emission computed tomography (SPECT) with technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO) was carried out in 20 melancholic patients before and after total sleep deprivation. Findings in 11 responders to total sleep deprivation (defined by > or = 40% improvement on the Hamilton Rating Scale for Depression) were compared with findings in nine nonresponders. On the basis of a semiquantitative evaluation of SPECT findings, responders showed relative hyperperfusion before sleep deprivation in the right anterior cingulate cortex and in the right and left fronto-orbital cortex and basal cingulate gyrus. Responders who showed > or = 50% improvement also showed hippocampal overactivation before sleep deprivation. It is possible that limbic overactivation may characterize depressed responders to total sleep deprivation as a distinct subtype. Another possibility is that the pattern of limbic hyperactivation reflects the increased number of bipolar patients in the responder group, with response to total sleep deprivation being only a covariate of this bipolar-unipolar distinction.

Reduced benzodiazepine receptor binding in panic disorders measured by iomazenil spect

We compared a group of nine patients with panic disorder (DSM-III-R) and depression with a matched control group of nine dysthymic patients without a previous or actual history of panic attacks or anxiety with iomazenil SPECT (single photon emission computed tomography) to evaluate panic-related abnormalities of the benzodiazepine receptor complex. The panic group had a significant decrease (p < .05, U-tests) in the regional activity index (RAI) in the following regions after 2 h: lateral inferior temporal lobes, right and left, medial inferior temporal lobes, left, inferior frontal lobes, right and left. All other regions investigated were not significantly different. The findings may be due to either regional blood flow differences or benzodiazepine receptor effects. The hypothesis that the effects are due to altered blood flow is confirmed to some extent by similar findings in the scans acquired after 10 min. Only the hypoactivity in the left lateral temporal region seemed to be independent of reduced blood flow in panic disorders.

A Knowledge Based System for Analysis of Gated Blood Pool Studies

A system for obtaining a complete diagnostic description of an image sequence taken in nuclear medicine from the human heart has been developed, implemented, and tested. The knowledge about these images is represented in a semantic net, conclusions are drawn by a production rule approach, and scoring of alternative diagnoses is based on fuzzy membership functions. On the low level, image pixels are smoothed and organ contours are extracted; these are the input for the high level processing. Tests with several image sequences gave correct descriptions as compared to the diagnosis of a physician.

Congenital Myocardial Sympathetic Dysinnervation (CMSD)—A Structural Defect of Idiopathic Long QT Syndrome

Concerning the path genetic mechanism of idiopathic long QT syndrome (LQTS), the hypothesis of a specific sympathetic imbalance has gained general acceptance, but its validity has never been proven. To test this hypothesis I‐123‐MIBG, an analogue of norepinephrine and guanethi‐dine, was used to provide scinfigraphic display of the efferent cardiac sympathetic innervation. Twelve members of four LQTS families fmean age 38.2 ± 17.2 years, eight males) and eight healthy volunteers (mean age 48.2 ± 13.3 years, five males) were studied by means of M23‐MTBG single photon emission computed tomography (SPECT). A quantitative analysis of all scans was performed. All scans of the healthy volunteers show a uniform tracer uptake with sometimes slightly decreased activity in the apex. (1) All patients with QTc > 440 msec (n = 5); (2) all, who had suffered from at least one episode of torsade de pointes, ventricular fibrillation (VF) or syncope (n = 5); and (3) all symptomatic patients with QTc prolongation (n = 4) have reduced or abolished (P < 0.02) MIBG uptakes in the inferior and inferior septal parts of the left ventricle (congenital myocardial sympathetic disintegration [CMSD]). Additionally, one female without symptoms or QTC prolongation (LQT) shows an abnormal MIBG SPECT similar to the one of her daughter, who has LQT and symptoms. One male without LQT, who had suffered from VF shows CMSD similar to his father, who has LQT, but no symptoms. All members of the families with normal MIBG SPECTs have neither LQT nor symptoms. In all families CMSD fulfills the criteria of autonomic‐dominant inheritance. Normal QTc‐interval predicted only in 57% normal cardiac sympathetic enervation in the present LQTS families. Therefore, quantitative I‐123‐MIBG SPECT enables to identify myocardial sympathetic disintegration as structural defect in LQTS. CMSD is associated with and without LQT and presents a pattern of autosomal‐dominant inheritance. LQT at rest or during exercise was specific (100%). but less sensitive (63%) in the assessment of CMSD than I‐123‐MIBG SPECT.

A test-retest study of cerebral blood flow during somatosensory stimulation in depressed patients with schizophrenia and major depression

SummarySix depressed patients with schizophrenia and 6 depressed patients with major depression were investigated before and during somatosensory stimulation (SS) with Tc-99m HMPAO SPECT. 8 controls were investigated only under resting conditions. The results can be summarized as follows: 1. Both psychiatric patient groups were hypofrontal (dorsolateral prefrontal cortex) compared to controls. 2. Hypofrontality was further enhanced by SS, significantly only in affective psychoses in the right inferior frontal lobe and in the right frontal hemisphere in total, in schizophrenia in the left dorsolateral prefrontal cortex. 3. Within the frontal lobes different regions were affected by SS in the two diagnostic groups. 4. In the right inferior parietal lobe SS response was significantly different in the two illnesses with schizophrenia showing a relative decrease, affective psychoses showing a relative increase of activity. 5. SS produced an increase of cerebral blood flow in subcortical regions (statistically significant contralateral to SS in thalamus and basal ganglia, ipsilateral to SS in cerebellum), a pattern which was common to all psychiatric patients. 6. Somatosensory cortex flow was not changed by SS. In conclusion, we could not fully confirm our hypotheses that similar blood flow abnormalities in different illnesses during SS are only caused by similarities in depressive psychopathology. Instead, depressed patients with schizophrenia were different from depressed patients with major depression in showing decreased activity in interrelating brain regions participating in an attentional network.

DISTRIBUTION OF RADIOLABELLED ANTI-CA125 MONOCLONAL ANTIBODY OC125-F(AB')2-FRAGMENT FOLLOWING RESECTION GUIDED BY ANTIBODIES (REGAJ) IN OVARIAN CANCER PATIENTS

Ovarian cancer is a highly malignant tumor of mainly postmenopausal women. The long‐term prognosis of this malignancy is largely determined by micrometastasis present at the time of second‐look surgery. In general, patients face a poor outcome. New radio‐immunoscintigraphic methods to target tumor tissue specifically via antigen‐antibody binding were developed. However, few studies so far investigated the pattern of in vivo distribution of radiolabelled mAbs and/or the specificity of antigen‐antibody interaction. In this study we examined the immunological interaction and distribution of 131 I‐OC125‐F(ab′)2‐fragment, an anti‐CA‐125 mAb, in patients with CA‐125 positive ovarian malignancies. Sixteen patients with primarily CA‐125 positive gynecological tumors underwent REGAJ surgery. Biopsies of tumor tissue and not tumor infiltrated tissue, serum, and ascites were sampled during or prior to REGAJ surgery, respectively. After preparation of tissue cytosols, samples were assessed for CA‐125 and radioactive uptake. By radiochromatography immunological analysis for presence of the target antigen CA‐125, the mAb 131I‐OC125‐F(9ab′)2‐fragment, and immune complexes was performed on different specimen. CA‐125 concentrations were higher in serum samples, ascites, and malignant tissue biopsies of malignoma patients compared to those without signs of malignant disease. CA‐125 was higher in the tissue cytosol than in the cell membrane fraction. Gel filtration revealed CA‐125 with moieties of 75,000 to < 600,000 d. Accumulation of radioactivity was more frequently associated with the presence of unbound 131I‐OC125‐F(ab′)2‐fragment or high molecular weight immune complexes. Radioactive uptake, however, was not confined to tissue of high CA‐125 expression. Moreover, both immune complex as well as 131I‐OC125‐F(ab′)2‐fragment could be isolated from cytosols of tissue not infiltrated by tumor cells as well. Our study demonstrates that the majority of CA‐125 is located intracellularly and thus inaccessible to 131I‐OC125‐F(ab′)2‐fragment per se. The uptake of 131I‐OC125‐F(ab′)2‐fragment into the cytosol of tumor‐free and malignant tissue samples prompts us to speculate that certain mechanisms for antigen‐specific and nonspecific cellular trafficking of mAbs do exist. We present a model to explain our observations. J. Clin. Lab. Anal. 11:94–103.

Myocardial damage assessed by indium-111-antimyosin: correlation with persistent enteroviral ribonucleic acid in dilated cardiomyopathy.

The persistence of enteroviral ribonucleic acid (RNA) in the myocardium has been implicated as a pathogenetic factor in idiopathic dilated cardiomyopathy. Enteroviral persistence may lead to myocardial cell membrane damage, resulting in increased uptake of antimyosin antibodies. To further evaluate this hypothesis, a direct comparison of myocardial antimyosin uptake with the presence of enteroviral RNA was performed in ten patients (one female, nine male; 53±8 years) with chronic dilated cardiomyopathy. Planar antimyosin images were obtained 48 h after the injection of indium-111-labelled antimyosin Fab. Using a region of interest technique, the heart to lung uptake ratio (HLR) was calculated as a semiquantitative parameter of myocardial tracer uptake. Cardiac catheterization was performed to assess left ventricular function and to obtain myocardial biopsy samples. In the biopsy samples, gene amplification by polymerase chain reaction (PCR) was used to specifically detect enteroviral RNA. In the ten patients, the left ventricular ejection fraction was 39%±11% and the end-diastolic volume 131±46 ml/m2. The HLR was 1.72±0.21 and showed no correlation with functional parameters. In two patients with a positive PCR consistent with persisting enteroviral RNA, the HLR was not higher than that in eight patients with a negative PCR (1.46±0.18 vs 1.78±0.18, respectively). These results suggest that increased uptake of111In-antimyosin in chronic idiopathic dilated cardiomyopathy cannot be explained by pure persistence of enteroviral RNA. Other pathogenetic factors such as myocardial autoantibodies or microvascular spasm may be responsible for myocyte membrane damage detected by antimyosin.