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Objectives: Central venous puncture is required for endomyocardial biopsy to identify rejection after cardiac transplantation. We evaluated our use of the Seldinger technique to determine the safety of this invasive method., Methods: In 42 immunosuppressed patients central venous puncture was performed after cardiac transplantation using the Seldinger technique for right heart biopsy. Together with physical examinations, chest X-ray and cardiac ultrasonography were performed during the inhospital follow-up. Outpatient follow-up continues and all reported adverse effects were evaluated by the attending cardiologist., Results: There were a total of 620 central venous punctures, most via the right internal jugular vein (77.9%). The planned puncture could not be performed in 3.2% of the cases and an alternative site was used. The femoral approach was associated with the longest radiation time. No severe adverse effects were observed and no complications (infection, large haematoma, pneumothorax, severe rhythm disorders) were recorded., Conclusion: Even in immunosuppressed patients frequently requiring central venous puncture, right heart endomyocardial biopsy can be safely performed to evaluate rejection.

The beta-adrenoceptor-adenylyl cyclase system was studied in heart ventricles from Wistar rats, cardiomyopathic (BIO 8262) and nonfailing control hamsters (CLAC) using the beta 1-adrenoceptor antagonist CGP 20712A. In radioligand binding studies, the majority of beta-adrenoceptors in ventricles from rats as well as from CLAC hamsters was of the beta 1-subtype (72.2% and 76.6%, respectively). In BIO ventricles a significant (CLAC vs. BIO, P < 0.05) reduction in the beta 1-subtype (62.9%) was found. In Wistar rats the subtype-mediated stimulation of adenylyl cyclase reflected the beta 1:beta 2 ratio as determined by binding studies. In hamster ventricles the effect of isoprenaline was mediated predominantly (CLAC) or exclusively (BIO) via the beta 2-subtype, indicating that cardiac beta 1-adrenoceptors were partly (CLAC) or completely (BIO) uncoupled from the adenylyl cyclase.

Endomyocardial biopsy in cardiac transplantation is still the most exact test (gold standard) to confirm or exclude a suspected rejection. Up to now, all available noninvasive tests suffer from a low sensitivity and specificity. For a further reduction of biopsies early available noninvasive methods are desirable. In the data presented a comparison between histological findings and heart volume measurements is shown in 40 patients (112 histological findings) after orthotopic cardiac transplantation. In 46 cases with no evidence of histological rejection the echocardiographically or radiologically determined heart volume was 869 +/- 142 ml/1.73 m2 body surface area, compared to 1026 +/- 178 ml/1.73 m2 in 29 cases with mild cardiac rejection. In 37 cases with a moderate or severe rejection heart volume as 1094 +/- 181 ml/1.73 m2. The diagnosis of a moderate or severe rejection by biopsy is combined with a heart volume above 950 ml/1.73 m2 with a sensitivity of 78% and a specificity of 73%. Intramyocardial edema as well as an increase in right and left ventricular volumes due to heart failure may be the causes for heart volume increase in rejection. Thus, heart volume measurement which can be performed easily during routine echocardiography gives additional information about whether a rejection has to be assumed or can be excluded. Today, sensitivity and specificity of the test does not allow a reduction of biopsy frequency. Further investigations are necessary to analyze the course of heart volume changes during an episode of rejection.

The effect of cyclosporine on the mean cytoplasmic free calcium concentration in electrically paced single cardiomyocytes from adult rats was studied. Cardiac myocytes were paced by electrical field stimulation with either 2 or 3 Hz in the presence of 5 micrograms/ml cyclosporine or the solvent cremophor. Exposure to cyclosporine during 40 minutes of electrical pacing caused irreversible hypercontracture in most cells, only 22.1% +/- 1.2% (mean +/- SEM) remained rod-shaped versus 64.1% +/- 3.2% in the solvent (p = 0.01). The cytoplasmic free calcium concentration was measured by means of digital image processing of fura-2 fluorescence. Electrical field stimulation increased the cytoplasmic free calcium from 69.7 +/- 5.4 to 124.9 +/- 24.5 nmol/L Ca2+ in the presence of the solvent and from 84.2 +/- 25.4 to 250.1 +/- 55.9 nmol/L in the presence of cyclosporine (p = 0.036 versus solvent). The data provide direct evidence that cyclosporine enhances the cytoplasmic free calcium concentration in single paced rat cardiomyocytes. These findings may be of importance in the consideration of a possible cardiotoxicity of cyclosporine.

Myocardial calcium overload in chronic heart failure is still a debatable issue. The aim of this study was to investigate the myocardial calcium content and intracellular calcium distribution in end-stage dilated cardiomyopathy. The explanted hearts of 13 patients (9 male, 4 female, mean age 49 ± 12 years) undergoing heart transplantation because of end-stage dilated cardiomyopathy were examined. Samples were obtained from the right and left ventricular free wall and from the septum. Calcium and magnesium content were measured by atomic absorption spectrophotometry. Ultrastructural calcium distribution was examined in dilated cardiomyopathy using the phosphate-pyroantimonate method. Ultrastructural calcium distribution was also examined in left ventricular biopsies obtained from 3 patients (male, mean age 47 ± 3.6 years) with nonfailing hearts. The number of mitochondrial calcium precipitates was estimated morphometrically by a point counting method. Myocardial calcium and magnesium content in dilated cardiomyopathy did not differ significantly among the right and left ventricles and septum ranging from 8.5 to 10.8 mmol/kg dry weight. The phosphate-pyroantimonate method visualized calcium precipitates being confined to the sarcolemma, T-tubules, intercalated disks, and mitochondria in both nonfailing myocardium and dilated cardiomyopathy. Because mitochondria may act as buffers of cytoplasmic calcium, mitochondrial calcium precipitates served as a criterion for a possible cellular calcium overload. No differences in the amount of mitochondrial calcium deposits were observed between dilated cardiomyopathy and nonfailing hearts. The data suggest that there is no global myocardial calcium overload in human eng-stage dilated cardiomyopathy., (Copyright © 1993. Published by Elsevier Inc.)

Apart from the eminent changes in the neurotransmitter systems of the central nervous system, a disturbance of the calcium ion concentration may be of significance in the pathophysiology of affective psychoses. The present paper deals with the contribution of calcium ions in the generation of affective psychoses and discusses the calcium antagonism as a new strategy in the treatment of the disease. The following topics will be described: 1. Disturbances of calcium metabolism in affective psychoses, 2. a comparison of lithium and carbamazepine effects, 3. clinical studies with organic calcium channel blockers in affective psychoses and 4. the role of calcium ions in affective psychoses.

Only few data exist concerning right ventricular function in the chronic stage after cardiac transplantation. Therefore, we investigated hemodynamic and right ventricular volumetric data by a computerized thermodilution Swan-Ganz catheter in 17 patients (median age: 53, range: 18-63 yr) at a median of 24 (4 to 44) months after cardiac transplantation during rest and supine bicycle exercise. Myocardial biopsy showed grade one or less according to the classifications of Billingham. Sixteen patients with coronary artery disease, but without prior myocardial infarction, served for comparison. While angiographic left ventricular ejection fraction was nearly identical in transplant recipients [77 (60-92)%, median (range)] and in patients with coronary artery disease [78 (64-94)%], right ventricular ejection fraction was lower (p < 0.001) in patients after cardiac transplantation [37 (16-58)%] as compared to patients with coronary artery disease [56 (46-62)%]. In transplant recipients right atrial pressure was significantly higher both at rest [10 (2-18) mmHg] and exercise [18 (8-30) mmHg] than in patients with coronary artery disease [5 (1-11) and 8 (3-18) mmHg]. Pulmonary capillary wedge pressure behaved similar in both groups. To further evaluate reasons for right ventricular impairment, a correlation analysis was performed. This showed a negative correlation between right ventricular ejection fraction and the time interval after transplantation (p < 0.0002). However, there was no correlation between right ventricular ejection fraction and acute rejection or a rejection score. In conclusion, right ventricular function may be severely altered in transplant recipients, in contrast to an only slight impairment of left ventricular function.

The hypothesis was tested that there are relationships between schizophrenic negative or deficit symptoms, the skin conductance nonresponding and an elevated amplitude of the postimperative negative variation (PINV). These variables were recorded in 16 chronic schizophrenics and 10 healthy controls. Clinical symptoms were assessed by the Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Frankfurt Complaint Questionnaire 3 and Chapman Questionnaire. In the patient group we found a significantly elevated PINV at Fz. Surprisingly, only one patient was a skin conductance nonresponder. PINV amplitude at Fz and the number of skin conductance responses to habituation were not correlated with negative or deficit symptoms inclding anhedonia. The hypothesis thus had to be rejected.

BASIC CONSIDERATION: Hypertrophic cardiomyopathy is defined as a primary myocardial disease associated with a hypertrophic non-dilated left ventricle with no other heart or systemic disease that might lead to hypertrophy of the left ventricle. The leading symptoms are effort-associated angina and dyspnea, rapid fatigue, dizziness and syncope., Main Points Discussed: The hemodynamic situation is characterized by a hyperdynamic systole and impaired diastole and left-ventricular filling. In the obstructive form, hypertrophy of the basal septum and an anteriorly moving mitral valve during systole result in an end-systolic reduction in the cross-section of the outflow tract associated with considerable intraventricular pressure gradients. Disturbances in the myocardial calcium metabolism are presently suspected to be causally involved in the diastolic function impairment.

30-day-old polymyopathic hamsters (strain BIO 82.62) were orally treated with either magnesium pyridoxal 5-phosphate glutamate 100 mg/kg, equimolar amounts of magnesium alone (MgCl2 55 mg/kg), or water b.i.d. for 30 days, or sacrificed before treatment. 60-day-old healthy hamsters (strain CLAC) served as controls. Magnesium pyridoxal 5-phosphate glutamate lowered the myocardial calcium content (42.8 +/- 13.1 mmol/kg dry weight) as compared to MgCl2 (70.3 +/- 11.9 mmol/kg dry weight) and water (72.7 +/- 13.6 mmol/kg dry weight). The serum and tissue lipid pattern did not differ between BIO 82.62 and normal hamsters except high serum cholesterol and triglyceride levels in 30-day-old BIO 82.62 hamsters. Myocardial necroses were influenced by neither magnesium pyridoxal 5-phosphate glutamate nor MgCl2. Cytochemical investigation of the ultrastructural calcium localization in the aorta revealed less calcium precipitates with magenesium pyridoxal 5-phosphate glutamate in media myocytes. It is concluded that magnesium pyridoxal 5-phosphate glutamate exerts a calcium antagonistic effect in the cardiomyopathy of the Syrian hamster which is related neither to the magnesium content of magnesium pyridoxal 5-phosphate glutamate nor to its lipid lowering activity.

Spontaneous intracerebral hemorrhages can occur in patients with severe amyloid angiopathy and other morphological signs of Alzheimer's disease (AD). We observed 15 patients in whom histological examination of brain tissue specimens obtained at surgery revealed characteristic congophilic amyloid deposits in subcortical arteries and/or nerve cells. Clinical follow-up examinations were carried out up to 9 years after diagnosis. In addition, three survivors from the operated group were investigated by neuropsychological testing and single photon emission computer tomography (SPECT) using Tc-99m-HMPAO for determination of regional cerebral blood flow (rCBF). SPECT could not differentiate between the "typical Alzheimer disease pattern" of bilateral temporo-parietal rCBF reduction and flow deficits resulting from previous hemorrhage. Intellectual functioning was found to be impaired to various degrees ranging from normal function to severe dementia (MMS test scores varied between 15 and 26 points); again, it was difficult to differentiate clinically between the nosologic entities mentioned above. On the basis of our present experience we cannot distinguish between brain dysfunction due to Alzheimer's disease and intracranial hemorrhage from amyloid angiopathy. This supports the idea that intracranial hemorrhage may only be one clinical manifestation of amyloid deposits, another one being "Alzheimer's disease" with varying preponderance.

Dysfunction of the vagal nerve, an early symptom in the development of autonomic neuropathy, can be assessed reliably by the beat-to-beat variation in heart rate. Patients after a cardiac transplantation are a unique model to investigate the beat-to-beat variation of a completely denervated heart. Heart rate and the beat-to-beat variation during normal and deep respiration were investigated in diabetic subjects with an autonomic neuropathy (n = 10), age and sex matched healthy controls (n = 10) and cardiac transplanted patients (n = 10). Further studies during pharmacological blockade of the parasympathetic nervous system with atropine were performed. In the denervated heart the coefficient of variation of the beat-to-beat interval was 0.38 +/- 0.02% during normal respiration, compared to 1.32 +/- 0.13% (P less than 0.0001) and 2.56 +/- 0.13% (P less than 0.0001) in the diabetic and control subjects, respectively. Administration of atropine (2 mg intravenously) decreased the coefficient of variation of the RR-interval to 0.73 +/- 0.09% in the diabetic patients (P less than 0.0005) and to 0.67 +/- 0.07% in the controls (P less than 0.0001), whereas the coefficient of variation remained unaffected in the cardiac denervated patients (0.39 +/- 0.02%). In the three groups an almost parallel increase of the RR-variation was observed during deep respiration at a rate of 6 breaths/min (from 0.38 +/- 0.02% to 1.99 +/- 0.38% in cardiac transplanted patients, P less than 0.0025; from 1.32 +/- 0.13% to 3.10 +/- 0.43% in diabetic patients, P less than 0.0025; from 2.56 +/- 0.13% to 5.42 +/- 0.94% in healthy controls, P less than 0.005). We conclude that a beat-to-beat variation of heart rate is present in the completely denervated heart. This RR-variation can not be influenced by a pharmacological blockade of the parasympathetic nervous system with atropine. The beat-to-beat variation increases during deep respiration not only in healthy controls but also in diabetic patients with autonomic neuropathy (partially denervated hearts) and cardiac transplanted patients (completely denervated hearts). This indicates an intracardiac mechanism in the modulation of heart rate.

Indium-111-labeled Fab fragment imaging using a murine antimyosin monoclonal antibody (Myoscint, Centocor, Leiden) was evaluated for efficacy in detecting cardiac allograft rejection. Diagnosis of rejection was made by endomyocardial biopsy with four to five samples taken for each procedure. Eighty-one studies were performed in 25 patients (21 men, four women, mean age 50 +/- 9 years) from 2 weeks to 45 months after cardiac transplantation. 0.5 mg of the monoclonal antibody labeled with 60 MBq Indium-111 (Antimyosin-Fab-DTPA) was administered i.v. Planar scintigraphic images were obtained in LAO 45 and anterior projections as well as "half-body-scintigrams" 48 h after injection. Using the regions-of-interest-(ROI)technique the relative uptake over the lung and the heart was determined and an index of In-111 uptake was calculated. A heart-to-lung ratio of 1.5 or higher was considered indicative for moderate to severe rejection. Specificity was 86% (nine false-positive In-111 studies in 68 negative biopsy studies), sensitivity was 85% (two false-negative In-111 studies in 13 pathological biopsy studies). It is concluded that the In-111 method has a high sensitivity and specificity in detecting heart transplant rejection and may be useful in the monitoring of patients in the chronic phase after heart transplantation. The 48-h delay in establishing the diagnosis limits the applicability in acute severe rejection.

The genetically inbred cardiomyopathic Syrian hamster provides a valuable model of congestive cardiomyopathy: myocytolytic necrosis at 30-50 days of age is followed by cardiac hypertrophy at 150-250 days, and finally by congestive failure and death at 250-350 days. Successful drug treatment has been reported in the prenecrotic stage, but not when started during congestive failure. The present study evaluated survival of the cardiomyopathic hamster treated with the new beta-adrenoceptor blocker nebivolol, which was initiated during congestive failure. Fifty animals (BIO82.62, either sex, age 200 days) were acclimated to an environmentally controlled room for 20 days, receiving food and water ad libitum; seven hamsters died, indicating development of congestive failure. The remaining animals were then randomly assigned to one of three groups: 15 animals received control food; food for the others was supplemented with nebivolol, yielding a daily intake of either 0.1 mg/kg (n = 14) or 1 mg/kg (n = 14). At the lower nebivolol dose, death rate was unaltered in comparison with controls. However, at 1 mg/kg, survival was markedly improved (p = 0.042). Nebivolol treatment, started during congestive failure, thus significantly delays mortality in the cardiomyopathic hamster.

The acute cardiotoxicity of cyclosporine was investigated in isolated cardiomyocytes from adult rats. In a first study, myocytes were incubated with CsA ranging from 1 to 10 micrograms/ml and paced by electrical-field stimulation. After 30 min of stimulation the number of surviving rod-shaped myocytes was significantly reduced at 2.5 micrograms/ml (77.9%) and 5 micrograms/ml CsA (64.2%) as compared with the drug vehicle methanol (88.8%, P less than 0.05) with a further decrease at 10 micrograms/ml CsA (30.1% vs. 81.2%, P less than 0.005). In a second study, with the use of digital image processing of fura-2 fluorescence, the mean intracellular free calcium concentration, integrated over 1 sec, of single myocytes in the presence of 5 micrograms/ml CsA, the solvent methanol, or pure Krebs Ringer Hepes buffer was measured. Starting 2 Hz field stimulation increased the intracellular free calcium concentration from 100.1 to 177.9 nM in buffer and from 145.7 to 200.6 nM calcium with methanol. In contrast, there was a 3-fold increase of the intracellular free calcium concentration with 5 micrograms/ml CsA from 128.8 to 376.1 nM calcium. The intracellular free calcium during electrical stimulation was significantly higher with CsA than with the solvent (376.1 nM vs. 200.6 nM, P less than 0.001). In a further study, myocytes were incubated with calcium ranging from 0.5 to 8 mM calcium in the presence of 5 micrograms/ml CsA or the solvent methanol and electrically stimulated. Here, with increasing extracellular calcium the number of rod-shaped myocytes decreased significantly with CsA as compared with the solvent (P less than 0.02). The data suggest that CsA exerts a dose-dependent toxic effect on isolated rat cardiomyocytes that depends on the extracellular calcium concentration. There is direct evidence that CsA increases the intracellular free calcium concentration in rat cardiomyocytes.

Five patients with hypertrophic cardiomyopathy developed left-ventricular dilatation and congestive heart failure during an observation period of 16-29 years. In one patient cardiac transplantation had to be performed. The initial predominant symptoms of outflow-tract obstruction and diastolic dysfunction developed into progressive left-ventricular systolic failure. The question of whether this is a well-defined subgroup of patients with hypertrophic cardiomyopathy, or whether hypertrophic cardiomyopathy turns into a phase of left-ventricular dilatation and failure after some years remains to be elucidated by long-term studies.

Left ventricular systolic and diastolic performance was evaluated by radionuclide angiography in 17 patients following cardiac transplantation and compared with normal persons. Both groups performed supine bicycle exercise during the investigation, the control group at 102 +/- 73 W and the transplanted patients at 61.2 +/- 15 W. The ejection fraction increased in the normal persons from 61 +/- 8 to 69 +/- 10% whereas in the transplanted patients it did not increase significantly. There were no relevant changes in systolic parameters during exercise in the transplant recipients. The changes in diastolic parameters were significantly smaller in transplant patients than in normals. After correction for heart rate-induced changes a significantly different time course of the systolic-diastolic sequence during the cardiac cycle became evident in the transplanted group at rest. During exercise the systolic-diastolic sequence during the cardiac cycle became similar in both groups. It is concluded that the reduced exercise capacity of patients in the late phase after cardiac transplantation is partially due to the absence of an EF increase and a limitation of diastolic reserve during exercise.

20 patients with neuropathic pain syndromes due to tumor-infiltration, who had not responded to conventional analgesics including strong opioids, received additional combination anti-convulsant and anti-depressant treatment. Pain amelioration occurred in all patients within median 46 h, and maximum effect was encountered within one week. Severe side effects were confined to three cases and were associated with carbamazepine treatment. Replacement by another type of anticonvulsants in 6 cases with either no response or intolerable side effects was successful in 5 patients, both in terms of efficacy and tolerability. One patient stopped taking AD/AC after 48 h.

From 1979 to 12/1990 795 organ transplants have been performed at our hospital (kidney n:737, liver n:23, heart n:35). Our data reveal vascular problems in 10 percent of the transplanted patients - not concerning the vascular anastomosis. The therapeutic approach should be determined interdisciplinary. Due to the low complication rate of operative or interventionel procedures in this patients, even relative indications--to improve "quality of live"--can be accepted.

Pancreatic enzyme secretion in rats has been shown to be stimulated differentially by the intestinal hormones secretin and cholecystokinin. Since it is unknown if activation of neural mechanisms have similar effects, it was the aim of the present study to examine in anesthetized rats the output of the pancreatic enzymes amylase, lipase, trypsin, and chymotrypsin before (15 min), during, and after (30 min each) vagal stimulation (5 ms, 10 V) with different frequencies (0.5, 5, 10, and 50 Hz). At 5 Hz, a maximal stimulation of all four enzymes was observed, with a peak towards the end of the vagal stimulation period. At 0.5 Hz, amylase, trypsin, and chymotrypsin were released not only in smaller quantities but also in a different time pattern (trypsin and chymotrypsin), with a maximum early during vagal stimulation. Lipase secretion remained unchanged at 0.5 Hz. At 10 Hz, the output of amylase, lipase, and trypsin was quantitatively less compared to 5 Hz. In contrast to stimulation at 0.5 and 5 Hz, the maximal enzyme output was reached after cessation of vagal stimulation (amylase and lipase). Chymotrypsin release did not change in response to vagal stimulation at 10 Hz. A frequency of 50 Hz had no influence on the secretion of any of the four enzymes determined. These data demonstrate that activation of the vagus nerves can lead to a differential release of pancreatic enzymes. The exact regulatory mechanisms of action are as yet unknown and remain to be determined.

Myocardial calcium overload was observed in a patient with giant cell myocarditis. The myocardial calcium content estimated by atomic absorption spectrophotometry amounted to 120 mEq/kg dry weight, and the von Kossa stain disclosed multiple foci with patchy calcifications of myocardial fibres. Cytochemical examination of the ultrastructural calcium localisation using the phosphate-pyroantimonate method showed considerable variation in the subcellular calcium distribution. In normal myocytes calcium precipitates were confined to the inner leaflet of the sarcolemma, T-tubules, intercalated disks, and sporadically to mitochondria. In contrast, extensive calcification of mitochondria and loss of sarcolemmal calcium was evident in necrotic myocytes. A number of grossly normal myocytes also showed an increase of calcium precipitates in slightly swollen mitochondria. These findings suggest that myocardial calcium overload in this case started in viable myocytes and was not merely a secondary phenomenon occurring after cell death.

The acute cardiotoxicity of cyclosporin A was studied in isolated cardiac myocytes from adult rats. In an initial series of 7 animals, myocytes were incubated with concentrations of cyclosporin A ranging from 1 microgram/ml to 50 micrograms/ml. Shape changes of untreated cells, cells treated with cyclosporin A and cells treated with the solvent of cyclosporin A, Tween 80/ethanol, were evaluated. After 8 hours and 16 hours, respectively, of incubation 92 +/- 4.3% and 72 +/- 8.7% of the non-treated control cells were still rod-shaped. Cyclosporin A, however, in a concentration of 5 micrograms/ml decreased the number of rod-shaped cells (79 +/- 3.2% at 8 hours and 51 +/- 3.5% at 16 hours) in comparison to the solvent (94 +/- 3.5% at 8 hours and 76 +/- 5.8% at 16 hours, P less than 0.02). This effect became more pronounced with higher concentrations of cyclosporin A. On the other hand, Tween 80/ethanol alone in higher concentrations also led to a reduced number of rod-shaped cells. In a second series of 7 animals using Tween 80/ethanol and methanol as drug vehicles, myocytes were incubated for 16 hours with 15 micrograms/ml of cyclosporin A in a calcium containing medium (1 mM) or a calcium free medium (10(-4) M ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid). The number of remaining rod-shaped cells was higher in the calcium free medium as opposed to the medium containing calcium when the cells were exposed to cyclosporin A. It is concluded that in the applied model cyclosporin A at high concentrations has an acute cardiotoxic effect which in part appears to be calcium related.

In a double-blind study 8 healthy male subjects received 100 micrograms human atrial natriuretic facotr-(99-126) (hANF) and NaCl0.9% in random order on different days. Following hANF injection a significant increase in cardiac beat-to-beat variation was observed (4.65% vs 5.95%). This shows that in vivo human atrial natriuretic factor stimulates cardiac parasympathetic activity in man.

Event related potential recording and psychometric evaluation of cognitive impairment were carried out on 21 patients with brain tumours, 21 patients with severe head injuries and 24 controls. The tumour and trauma patients who met the psychometric inclusion criteria for dementia, but not the non-demented patients, had significantly longer N2 and P3 latencies than the controls. In assessing individual patients P3 latency correctly differentiated between demented and non-demented patients in 81% of cases (for N2 latency 77%). Particularly P3 latency may provide a practical and objective measure of mental impairment in neurosurgical disorders producing dementia. Marked asymmetry in N2 and P3 amplitudes between hemispheres was observed in a number of cases. No significant relationship was found between diminution of N2 and P3 components and side of lesion.

Event-related potential recording and neuropsychologic testing were carried out on 18 severely head-injured patients and on a control group. At early stages of injury the patients had prolonged P3 latencies and reduced psychometric scores. In the assessment of individual patients the P3 latency proved to be a measure that diagnosed cognitive impairment with clinically acceptable levels of accurate classification. On retesting 4.6 +/- 1.6 months after trauma, normal values were found for the neuropsychologic measures and a residual latency prolongation for P3, indicating the P3 latency to be a sensitive index of subtle residual brain dysfunction due to head injury.

A case is reported of right ventricular outflow obstruction caused by hypertrophic cardiomyopathy. The pressure gradient between the inflow tract and the outflow tract of the right ventricle was 84 mm Hg. Resection of the hypertrophic muscle bundles practically eliminated the obstruction leaving only an insignificant subvalvular gradient of 2 mm Hg. Histologic examination revealed cardiac muscle cell hypertrophy and disorganization.

Forty-three patients with severe visual impairment due to bilateral eye disease were assessed for visual hallucinations, 28 of them after eye surgery. Ages ranged between 65 and 93 years and none of the patients had any psychiatric disorder. Five of the 43 patients were diagnosed as cases with Charles Bonnet syndrome reporting visual hallucinations that had developed in the course of sight deterioration. There was strong indication that sensory deprivation was an essential pathogenetic factor for this phenomenon. Three of the 28 patients assessed following eye surgery who had no history of hallucinatory phenomena experienced visual hallucinations on the 2nd postoperative day without showing any other psychiatric symptoms. The various conditions associated with visual hallucinations are discussed that may be of relevance to the ophthalmologist.

The distribution of glutamic acid decarboxylase (GAD) immunoreactive neurons, fibres and punctae in sector CA 1 of the adult human Ammon's horn was studied in Vibratome sections (40 micron thick) of tissue obtained at surgery and autopsy. On light microscopical examination, the material did not show pathological changes. The antibody was visualized by the unlabelled antibody enzyme method. GAD-immunoreactive neurons, fibres and punctae were present in all layers. Most immunoreactive neurons were located in the stratum pyramidale and stratum lacunosum. Their size ranged from 8 microns in the stratum lacunosum to about 50 microns in the stratum oriens. The somata offered a wide range of shapes, multiform to fusiform with the long axis aligned parallel or vertically to the alveus. All somata belonged to the heterogeneous group of non-pyramidal neurons. The dendrites either radiated in all directions or tended to run in two opposite directions. After bleaching the chromogen and staining for lipofuscin pigment granules and basophilic material, it turned out that within the stratum pyramidale all formerly GAD-immunoreactive neurons belonged to the group of lipofuscin-laden non-pyramidal neurons. Within the other layers, a few formerly GAD-immunoreactive neurons were devoid of lipofuscin pigment. The highest density of GAD-immunoreactive punctae was found in the stratum lacunosum. In addition to numerous GAD-immunoreactive punctae in the pyramidal layer and in the stratum radiatum there were thin GAD-immunoreactive fibres of varying length extending into various directions.

Left ventricular function was investigated by radionuclide ventriculography in 13 patients (11 male, two female) with hypertrophic cardiomyopathy, aged from 22-57 years (mean 45.5 years) at rest and during exercise. Ten patients had hypertrophic obstructive cardiomyopathy with maximal left ventricular outflow tract gradients of 64-290 mmHg (mean 147 mmHg). Left ventricular enddiastolic pressure of all patients ranged from 8-35 mmHg (mean 21 mmHg). Radionuclide ventriculography was performed without therapy, after acute application of a single oral dose of gallopamil (50 mg), and after longterm treatment for 3 weeks (50 mg tid). Ejection fraction at rest after single dose increased from 69.2% to 72.9% (p less than 0.02), peak ejection rate (PER) increased from 333.5 to 362.0/s (p less than 0.01) and peak filling rate (PFR) from 284.5 to 316.5/s (p less than 0.02). Under exercise single dose as well as longterm treatment led to a slight but significant shift in the ratio of PFR/PER (from 1.02 to 1.12 after single dose [p less than 0.04], and to 1.18 with longterm treatment [p less than 0.03]). There was no correlation between the individual response to gallopamil treatment and histopathological parameters such as hypertrophy or fibrosis. These data demonstrate that gallopamil in patients with hypertrophic cardiomyopathy leads to an improvement mainly in left ventricular diastolic function which appears to be most effective under exercise.

Combined Golgi/pigment studies revealed that pyramidal neurons and non-pyramidal cells of the Ammon's horn of the human adult can be distinguished from each other by their characteristic lipofuscin pigment deposits. In sector CA1, both the typical pyramidal neurons and the modified forms of pyramidal cells contain a modest amount of fine lipofuscin granules while non-pyramidal cells are either pigment-laden or devoid of lipofuscin deposits. Strips running through the whole depth of the pyramidal cell layer and the stratum oriens of CA1 were examined and all nucleolated nerve cells present within these strips were classified and counted (16 brains, age range from 28 to 69 years). Of the 18,510 neurons classified, 16,765 were pyramidal cells, including their modified versions, and 1,745 were non-pyramidal cells. The pyramidal cells, accordingly, were intermixed with 9.4 +/- 1.0% non-pyramidal neurons. The data presented provide a basis for investigation of the aging and diseased human brain.

We report on 2 children aged 13 and 14 months with congenital central alveolar sleep apnea which showed depression of respiratory drive during sleep resulting from dysfunction of central chemoreceptors. Hypoventilation was found to be more severe during NREM sleep (minimum of alveolar ventilation in stages 3/4) than during REM sleep. During NREM sleep arousal responses to hypoxia proved to be an important factor in influencing the level of alveolar ventilation and in preventing fatal asphyxia.

Event-related potential recording (component N1, P2, N2, and P3) and neuropsychological assessment of cognitive impairment were carried out on 15 patients with brain tumour, 15 patients with severe head injury and 24 controls. The tumour and trauma patients had significantly lower psychological test scores, smaller N1 amplitudes and longer N2 and P3 latencies than normals. For the tumour and trauma patients significant correlations were found between N2 and P3 latency and the Mini-Mental State test and memory tests. For individual patients abnormally increased N2 and P3 latency was found to occur in association with abnormally reduced neuropsychological test scores. N2 and P3 latency proved the only electrophysiological variables examined which provided a measure of cerebral functioning correlating with the psychometric variables. N2 and P3 latency may be regarded as a useful diagnostic test for cognitive impairment especially in patients with motor handicaps, to whom neuropsychological tests cannot be administered.

Eleven patients with hypertrophic cardiomyopathy were investigated by repeated radionuclide ventriculography. Nine of them were studied for the first time while under long-term treatment for 14 to 84 months. In all eleven patients radionuclide ventriculography was performed after a withdraw of verapamil for at least 14 days or before the onset of therapy respectively (control period). A third investigation was carried out 60 to 90 min after acute administration of 90 mg oral verapamil. A last radionuclide ventriculography was performed following 2 weeks of therapy with 480 mg oral verapamil. After acute administration heart rate significantly increased from 69 +/- 10 to 80 +/- 15/min. EDV was in the normal range. Left ventricular global ejection parameters showed no significant changes except for minimal decrease in ejection time from 309 +/- 29 to 278 +/- 50 ms after acute verapamil administration. The sectorial ejection fraction improved in apical sectors in relation to the basal one, while the global EF remained constant. The ventricular global peak filling rate increased significantly from 283 +/- 61 to 325 +/- 64%/EDV/s after acute administration of verapamil and the sectorial peak filling rate increased in apical sectors compared to basal sectors following acute administration as well as long-term therapy. After withdrawal of verapamil, six out of 11 patients showed a homogeneous left ventricular delay of contraction by means of the Fourier phases which were normalized under short- and long-term verapamil treatment. In conclusion, verapamil caused a marked improvement of the left ventricular contraction delay without significant changes in global systolic function.

Two cases of Charles Bonnet Syndrome (CBS) showing an unusual history are reported. In a 67-year-old man visual hallucinations developed 38 years after bilateral optic nerve damage due to methyl alcohol poisoning. A 78-year-old woman suffering from bilateral advanced cataract experienced visual hallucinations which ceased after improvement of vision resulting from cataract extraction. Sensory deprivation and--possibly--central neurophysiological disturbance are to be regarded as important pathogenetic factors. Signs of cerebral dysfunction which could be relevant to the pathogenesis of CBS were revealed by the EEG.