Ch. Müller

DC-potential shifts and regional cerebral blood flow reveal frontal cortex involvement in human visuomotor learning

SummaryIn the present study, two different physiological parameters were measured to describe brain activity related to visuomotor learning: performance-related DC-potential shifts and regional cerebral blood flow (rCBF) by Tc-99m HMPAO brain SPECT (Single Photon Emission Computerized Tomography). Visuomotor learning was required in a conflicting situation: a visual target moved on a screen and had to be tracked by moving the right hand in an inverted fashion (IT), e.g. movements of the target to the right side required hand movement to the left and vice versa. Compared to a normal, non-inverted control task (T), IT required the development of a novel motor program and the prevention of returning to routine direct pursuit. These additional demands in IT caused a relative hyperperfusion in regions including the middle frontal gyri, frontomedial cortex (including the supplementary motor area, SMA), right basal ganglia (caudate-putamen) and left cerebellum. Correlations of rCBF values between the middle frontal gyrus and basal ganglia may indicate a functional relation between these two brain structures. Visuomotor performance was accompanied by slow negative DC-potential shifts. In frontal and to a lesser degree in central recordings, amplitudes of DC-negativity were larger in IT than they were in T. This additional frontal negativity covaried with the success of learning. Results substantiate, now using a dual approach, previous suggestions that the frontal lobe plays an important role in visuomotor learning.

Plasma Atrial Natriuretic Factor in Cirrhotic Patients With Ascites: Effect of Peritoneovenous Shunt Implantation

Human atrial natriuretic factor (ANF) levels were measured before and after peritoneovenous shunt implantation in 10 cirrhotic patients with ascites, in whom sodium retention is a major clinical problem. The mean preoperative plasma level of ANF was 82 ng/L (normal range, 5-80 ng/L). Peritoneovenous shunting resulted in a significant rise in plasma ANF to 308 ng/L (p less than 0.0025) immediately after operation. This was followed by a constant fall until the seventh postoperative day, when mean plasma ANF was still significantly elevated (149 ng/L) compared with the preoperative value (p less than 0.01). Three months after shunt implantation mean plasma ANF had returned to the preoperative level (75 ng/L). Mean sodium excretion increased from 2.6 mEq/h preoperatively to 10.2 mEq/h at the second postoperative day (p less than 0.025). No direct relationship was noted between changes in plasma ANF level and changes in urinary sodium excretion after shunt implantation. These data demonstrate an intact ANF release response to intravascular volume expansion in cirrhotic patients with ascites, but exclude ANF as the diminished natriuretic factor as proposed by the overflow theory of ascites formation. Sodium excretion and fluid retention seem to be the result of vascular underfill and fluid maldistribution, and hormonal changes are likely to be secondary to them.

Decreased serum osteocalcin levels in patients with liver cirrhosis.

Serum levels of osteocalcin (OC) have been found to be a specific biochemical parameter of bone formation. We measured serum levels of osteocalcin, parathyroid hormone (PTH) and 25-hydroxyvitamin D (25(OH)D) in 49 patients with liver cirrhosis, who are known to have an increased prevalence of metabolic bone disease, and a matched control group (n = 35). Serum levels of OC were significantly decreased in the patients with liver cirrhosis when compared to control subjects (P less than 0.001). Serum levels of 25(OH)D were decreased (P less than 0.001), whereas no statistical difference was found between the serum levels of PTH in the patients with liver cirrhosis and those of the controls. In a subgroup of 23 patients with cirrhosis of the liver and 34 control subjects, the bone mineral content (BMC) of the non-dominant forearm was determined by single photon absorptiometry. BMC was significantly lower in the patient with liver cirrhosis than the control subjects (P less than 0.04). Our data demonstrate vitamin D deficiency, decreased bone formation and a decreased BMC in patients with liver cirrhosis.

Increased serum concentrations of cholesterol and triglycerides in the progression of breast cancer

SummaryThe course of serum concentrations of cholesterol and triglycerides was investigated in patients with advanced breast cancer. The patients studied were divided into two groups according to their clinical status: group-I consisted of 51 patients who already had metastases at the start of the investigation, but progressed further during the time of observation; group-II consisted of 14 patients in remission who experienced recurrence of disease while under observation. In group-I, 28 patients (54.9%) were found to have normal serum triglyceride levels at the beginning of the observation period; 22 patients (78.6%) from this group experienced a significant (P<0.0001) increase above the normal range upon further disease progression. Similarly, serum cholesterol levels were normal in 32 patients (62.8%) at the start of the investigation, but increased significantly (P<0.0001) above the normal range upon disease progression. In group-II, 8 patients (57.2%) had normal serum triglyceride levels at the beginning of the observation period, but the levels inreased in 4 patients (50%) significantly (P<0.005) upon the occurrence of metastases. Within the same group, a significant increase (P<0.001) of initially normal serum cholesterol levels was found in 4 (44.9%) out of 9 patients. In summary, a rise in serum levels of triglycerides and/or cholesterol should receive increased attention and could indicate progression or recurrence of breast cancer.

Soluble interleukin-2 receptor and soluble CD8 antigen in active rheumatoid arthritis

Concentrations of soluble interleukin-2 receptor (sIL-2R) and of soluble CD8 antigen (sCD8) in sera and in supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) derived from patients with active rheumatoid arthritis (RA) were studied. sIL-2R concentrations in sera derived from patients with RA (1484 +/- 382 U/ml) were significantly higher than in sera derived from healthy controls (380 +/- 110 U/ml; P less than 0.0005). In contrast, supernatants of PHA-stimulated PBMC derived from patients with RA contained similar amounts of sIL-2R (727 +/- 467 U/ml) as those derived from healthy control individuals (833 +/- 508 U/ml; P greater than 0.1). When investigated for the presence of sCD8 antigen, sera derived from patients with RA contained significantly lower amounts (30 +/- 28 U/ml) than sera derived from healthy controls (405 +/- 136 U/ml; P less than 0.0005). Similarly, PHA stimulation of PBMC derived from patients with RA resulted in a significantly lower production of sCD8 (35 +/- 46 U/ml) as compared to the one obtained by PHA stimulation of PBMC derived from healthy controls (177 +/- 59 U/ml; P less than 0.0005). This difference could not be explained by a lower proliferative response to PHA by PBMC derived from patients with RA (21,474 +/- 14,022 cpm) as compared to healthy controls (29,549 +/- 11,188 cpm; P greater than 0.05). Our data demonstrate that PBMC derived from patients with active RA differ from PBMC derived from healthy individuals concerning their ability to produce sIL-2R and sCD8.

Initiation of visual-guided random saccades and remembered saccades in parkinsonian patients with severe motor-fluctuations.

SummaryWe studied the initiation of saccades to visual-guided random time and remembered targets in a group of nine Parkinsonian patients with severe motor fluctuations and in 9 age matched control subjects. In contrast to a marked skeletomotor improvement during the “on” condition, saccadic latencies for both visual-guided random saccades and remembered saccades were increased in the patients during the “on” condition compared to the “off” condition. This result of dissociation between skeletomotor and oculomotor function indicates that common concepts of saccadic initiation in parkinsonian patients do not hold true in patients with severe fluctuations since dopaminergic stimulation seems to increase saccadic latencies in these patients.

Evaluation of prostaglandin-receptors in human and rat liver: Interspecies differences at the prostaglandin receptor-level

The properties of PGE1-, PGE2- and iloprost (stable PGI2-analogue)-binding sites on normal human and rat liver surface cell membranes were investigated. The specific binding of [3H]PGE1 to human (rat) liver surface cell membranes could be displaced most effectively by unlabeled PGE1 (IC-50:2.5 +/- 1.7, (6.1 +/- 2.1) microM) and the specific binding of [3H]PGE2 by unlabeled PGE2 (IC-50: 1.9 +/- 0.9 (2.0 +/- 0.8) microM. The Scatchard analysis on [3H]PGE1- as well as on [3H]iloprost-binding was curvilinear whereas it was clearly linear on [3H]PGE2-binding in both the species. The high-affinity [3H]PGE1-sites showed a Bmax of 36.3 +/- 5.2 (21.3 +/- 4.3) fmol/mg protein and a Kd of 2.1 +/- 1.8 (1.9 +/- 0.7) nM, the low-affinity [3H]PGE1-sites a Bmax of 93.4 +/- 18.2 (86.1 +/- 13.2) fmol/mg protein and a Kd of 10.5 +/- 2.9 (15.1 +/- 3.2) nM. The high-affinity [3H]iloprost-sites exhibited a Bmax of 71.4 +/- 13.9 (35.9 +/- 8.2) fmol/mg protein and a Kd of 4.1 +/- 1.2 (1.7 +/- 1.8) nM, the low-affinity [3H]iloprost-sites a Bmax of 217.3 +/- 42.1 (142.9 +/- 17.8) fmol/mg protein and a Kd of 16.3 +/- 4.9 (9.2 +/- 7.2) nM. The [3H]PGE2-sites showed a Bmax of 135.4 +/- 51.9 (38.8 +/- 7.4) fmol/mg protein and a Kd of 16.2 +/- 3.2 (2.5 +/- 1.2) nM. It is assumed that prostaglandins of the E-series are promising substances in the regulation of human and rat liver function since liver cells are able to bind reasonable amounts of these substances in a high affinity manner. However, interspecies differences in the affinity of the prostaglandins to their receptor-sites make it strange to assume that the same biological findings claimed several times for the rat liver are relevant for human too.

Serum osteocalcin levels are decreased in patients with acute viral hepatitis.

In 16 patients with acute viral hepatitis and 32 sex- and age-matched control subjects the serum levels of osteocalcin, a biochemical parameter of bone formation, as well as the serum levels of parathyroid hormone, 25-hydroxyvitamin D, calcium and phosphorus were measured. The serum levels of osteocalcin (P less than 0.0001) and parathyroid hormone (P less than 0.0001) were significantly lower when measured at the time of maximal aminotransferase levels in the patients with hepatitis than in the control subjects. In contrast, the serum levels of calcium and 25-hydroxyvitamin D were similar in the patients and the controls. In nine patients with acute hepatitis measurements of the biochemical bone metabolism parameters were performed after normalization of the liver enzymes. In these patients a significant increase of serum osteocalcin levels towards normal values (P less than 0.0005) was found, parathyroid hormone levels tended to increase. Our data suggest an alteration of bone metabolism in patients with acute viral hepatitis. Bone formation as reflected by serum osteocalcin levels seems to be decreased in acute hepatitis and returns to normal after recovery from hepatitis.

Defective interferon-augmented natural killer cell activity in patients with metastatic malignant melanoma

SummaryUnstimulated and interferon(IFN)-stimulated natural killer cell (NK) activity was investigated in patients with malignant melanoma prior to the removal of the primary melanoma (stage I disease) or in patients with melanoma metastases. Unstimulated as well as IFN-stimulated NK activities, directed against the primarily NK-sensitive K562 cell line, were found not to differ significantly from the NK activity of healthy control subjects. In contrast, IFN-stimulated NK activity directed against the primarily NK-insensitive Chang hepatoma and JY cell lines was significantly lower in patients with metastatic melanoma than in patients with non-metastatic diasease (Chang hepatoma cell line: P<0.02; JY cell line: P<0.0017) and-in experiments using the JY cell line — than in healthy controls (P<0.01). Stage I melanoma patients did not differ in their IFN-induced NK activity from healthy control subjects using Chang hepatoma and JY cell lines. Finally, the IFN-induced increase in NK activity directed against primarily NK-insensitive target cell lines was significant in stage I melanoma patients and in healthy controls (P<0.01, respectively), but not in patients with metastatic melanoma (P>0.5). We thus conclude that patients with metastatic malignant melanoma exhibited a defect in IFN-augmented NK activity directed against primarily NK-insensitive targets.

Diagnostik des peritoneovenösen Shuntverschlusses

Reaccumulation of ascitic fluid after peritoneovenous shunt implantation demands accurate diagnostic procedure. Between 1973 and 1985 81 peritoneovenous shunts have been implanted at the IInd Surgical Department of the University of Vienna. In the same time 34 reoperations in 17 patients have been performed for reasons of shunt-dysfunction. Besides thorax x-ray, diagnosis was established in 11 cases by means of Doppler ultrasound investigation, in 26 cases by technetium scan and in 15 cases by shunt angiography. Shuntography proved to be the method of choice, with no false results. Doppler ultrasound results were unclear in a high percentage, thus this method is not used any more.SummaryReaccumulation of ascitic fluid after peritoneovenous shunt implantation demands accurate diagnostic procedure. Between 1973 and 1985 81 peritoneovenous shunts have been implanted at the IInd Surgical Department of the University of Vienna. In the same time 34 reoperations in 17 patients have been performed for reasons of shunt-dysfunction. Besides thorax x-ray, diagnosis was established in 11 cases by means of Doppler ultrasound investigation, in 26 cases by technetium scan and in 15 cases by shunt angiography. Shuntography proved to be the method of choice, with no false results. Doppler ultrasound results were unclear in a high percentage, thus this method is not used any more.ZusammenfassungDas Wiederauftreten von Ascites nach peritoneovenöser Shuntimplantation erfordert eine genaue diagnostische Abklärung. 81 Shunts wurden von 1973 bis 1985 an der II. Chirurgischen Universitätsklinik in Wien implantiert. Im selben Zeitraum mußten bei 17 Patienten insgesamt 34 Revisionen wegen Shuntdysfunktion durchgeführt werden. Als diagnostische Methode zur Prüfung der Funktion und Lokalisation der Verschlußursache wurde neben Thoraxröntgen eine Doppler-Ultraschalluntersuchung in 11 Fällen, ein Technetium-Scan in 26 Fällen sowie eine angiographische Shuntdarstellung in Verbindung mit einer Messung des zentralvenösen Drucks in 15 Fällen angewandt. Als aussagekräftigste Methode erwies sich die Shuntographie. Die Doppler-Ultraschalluntersuchung haben wir wegen ihrer häufig unklaren Ergebnisse ganz verlassen.