Pulsatility Index in the Basal Ganglia Arteries Increases with Age in Elderly with and without Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: Cerebral small vessel disease contributes to stroke and cognitive impairment and interacts with Alzheimer disease pathology. Because of the small dimensions of the affected vessels, in vivo characterization of blood flow properties is challenging but important to unravel the underlying mechanisms of the disease. MATERIALS AND METHODS: A 2D phase-contrast sequence at 7T MR imaging was used to assess blood flow velocity and the pulsatility index of the perforating basal ganglia arteries. We included patients with cerebral amyloid angiopathy (n = 8; identified through the modified Boston criteria), hypertensive arteriopathy (n = 12; identified through the presence of strictly deep or mixed cerebral microbleeds), and age- and sex-matched controls (n = 28; no cerebral microbleeds). RESULTS: Older age was related to a greater pulsatility index, irrespective of cerebral small vessel disease. In hypertensive arteriopathy, there was an association between lower blood flow velocity of the basal ganglia and the presence of peri-basal ganglia WM hyperintensities. CONCLUSIONS: Our results suggest that age might be the driving factor for altered cerebral small vessel hemodynamics. Furthermore, this study puts cerebral small vessel disease downstream pathologies in the basal ganglia region in relation to blood flow characteristics of the basal ganglia microvasculature.

Vascular metabolic dysfunction and lipotoxicity.

The purpose of this study was to determine the role of lipotoxicity in vascular smooth muscle (VSM). C(1)-BODIPY 500/510 C(12) used to assess the ability of VSM A7r5 cells to transport long-chain fatty acids showed that lipid transport did not appear to limit metabolism. Thin layer chromatography revealed that storage of transported fatty acid occurred primarily as mono- and diglycerides and fatty acids but not as triglycerides. We used lipid-induced apoptosis as a measure of lipotoxicity and found that 1.5 mM palmitate (6.8:1) bound to albumin resulted in a 15-fold increase in the number of apoptotic cells compared to the control at 24 hours. This apoptosis did not seem to be due to an increase in reactive oxygen species (ROS) since VSM cells incubated in palmitate showed less ROS production than cells incubated in albumin only. Similar exposure to oleate did not significantly increase the number of apoptotic cells compared to the control. Oleate actually significantly attenuated the apoptosis induced by palmitate, suggesting that unsaturated fatty acids have a protective effect on cells undergoing palmitate-induced apoptosis. These results suggest that vascular smooth muscle is vulnerable to lipotoxicity and that this lipotoxicity may play a role in the development of atherosclerosis.

[Long-term course of chronic polyarthritis under basic drug therapy]. / Langzeitverlauf der chronischen Polyarthritis unter Basismedikation.

A retrospective analysis was undertaken of 31 patients with classical or proven chronic rheumatoid arthritis (CRA) who had been on a regimen of basic medication (gold salts, D-penicillamine, chloroquine, azathioprine--alone or in combination). Disease activity was checked by clinical, biochemical, immunological and radiological criteria. The laboratory results could not be altered by the basal medication and there was no relationship with the clinical and radiological findings, except for immunological results. None the less, the clinical symptoms improved under basal medication, even though the functional index got worse. The degree of joint destruction at the beginning and end of the observation period was markedly higher for seropositive than sero-negative cases, without significant differences in the rate of progression of joint destruction. Thus, definite long-term remission was achieved regarding the inflammatory changes but not the progressing joint destruction.

[Immunomodulating therapy in chronic polyarthritis with thymopentin. A multicenter placebo-controlled study of 119 patients]. / Immunmodulierende Therapie der chronischen Polyarthritis mit Thymopentin. Eine multizentrische placebokontrollierte Studie an 119 Patienten.

In a multicenter, placebo-controlled and randomized double-blind trial 119 patients with rheumatoid arthritis were treated with thymopentin, an immunoregulating drug. The data of 107 patients were complete enough to be evaluated: 51 were given intravenous injections over ten minutes of 50 mg thymopentin three times weekly, 56 were similarly treated with a placebo solution. Significant improvement of five among nine clinical criteria were obtained with thymopentin after the third week of treatment. The response rate (improvement of a clinical parameter by at least 40%) was significantly greater for all clinical parameters in the thymopentin group. Regression to a functionally more favourable class (Steinbrocker's classification) occurred in seven thymopentin-treated, but in none of the placebo-treated patients. The improvement gradually subsided over four weeks after the end of treatment. There were no changes during the trial with respect to immunological, biochemical or haematological findings. Except for one systemic allergic reaction there were no side effects.

[Follow-up study in chronic polyarthritis as represented in roentgen image]. / Verlaufskontrolle der chronischen Polyarthritis im Röntgenbild.

Thirty-one patients with chronic polyarthritis under medical treatment had x-rays of their hands performed at the beginning of the illness and after seven years, on average. The findings were compared with clinical and biochemical data. Despite treatment, there was marked progression in the periarticular destructive changes, although the clinical features had improved. The extent of periarticular destruction was significantly greater amongst seropositive than amongst seronegative patients, both at the beginning and the end of the study, but there was no significant difference in the rate at which this progressed. It was not possible to demonstrate a statistically significant correlation between the radiological appearance of the joints and the clinical and laboratory findings.

[Right atrial and ventricular thrombus formation in advanced left-side hypernephroma]. / Rechtsatriale und rechtsventrikuläre Thrombusbildung bei fortgeschrittenem linksseitigem Hypernephrom.

Hypernephromas may give rise to extensive thrombus formation in the inferior vena cava. In a 70-year-old female patient, two-dimensional echocardiography revealed a well-defined mass (2 X 2 cm in dimension) in the right atrium with occlusion of the tricuspid valve and thrombo-embolic material spreading from the inferior vena cava to the right atrium. This finding was confirmed by computed tomography and cavography. Computed tomography of the abdomen detected a large left-sided renal tumour and thrombotic occlusion of the whole vena cava. The patient was not willing to undergo surgery and the masses of thrombo-tumorous material in the right atrium and ventricle spread rapidly. Meanwhile a spontaneous recanalization of the oval foramen occurred. The patient died from massive pulmonary embolism. Only the signs and symptoms of right heart failure with confirmed thrombus formation in the right atrium led to the diagnosis of hypernephroma.

[Pulsed Doppler echocardiography in prosthetic aortic and mitral valve replacement]. / Gepulste Doppler-Echokardiographie bei prothetischem Aorten- und Mitralklappenersatz.

In 94 subjects with normally functioning heart valve prostheses (51 aortic and 43 mitral valve prostheses) and in 35 patients with intact aortic and mitral valves, blood flow velocity within the heart and the aortic root have been recorded using pulsed Doppler velocity studies in patients with diseased valves of the left heart. In addition, a further 7 patients were investigated using invasive catheter tip velocitometry, pre- and postoperatively. The preversus postoperative changes of maximum velocity and acceleration is characterized as follows: postoperative flow velocity tracings show approximately normal profiles comparable to normal valve function. Turbulence formation is diminished and the steep uptroke of the normal flow pattern is restituted. Differences in transprosthetic blood flow patterns dependent on the implanted prosthesis model can be defined. Bioprostheses, in particular the Carpentier-Edwards device, reliably approximate normal amplitude-time characteristics. This is also true for the St. Jude Medical prosthesis with central flow properties. Velocitometric signs of valve dysfunction were detected in 9 patients: sensitivity was 100%; specificity ranged from 76% in aortic to 96% in mitral prostheses. Pulsed Doppler echocardiography therefore is a useful complement in the non-invasive haemodynamic tools and can be repeatedly applied to a patient with prosthetic cardiac valve replacement.

[Reduction of regurgitation in aortic and mitral insufficiency by captopril in acute and long-term trials]. / Reduktion der Regurgitation bei Aorten- und Mitralinsuffizienz durch Captopril im Akut- und Langzeitversuch.

Afterload reduction is an accepted therapeutic principle in the management of acute aortic (Ai) and mitral insufficiency (Mi). The question whether acute and chronic converting-enzyme inhibition by captopril has a beneficial hemodynamic effect in chronic Ai and Mi has been investigated in 17 patients with Ai and 10 with Mi. Ejection and regurgitation fraction (RF) were measured by radionuclide ventriculography (RNV) before, after 25 mg captopril and after 3-5 months of long-term treatment. The humoral response of the renin-angiotensin system (RAS) was quantified by analysis of angiotensin I and II. Captopril lowered under acute and chronic treatment RF in Ai and Mi by 32%. Angiotensin II levels decreased by the same order of magnitude. Acute and chronic vasodilation was followed by a distinct but well tolerated fall in blood pressure, especially in patients with Mi. These favourable hemodynamic effects of captopril make this therapy an adjunct but not an alternative to valve replacement.

Captopril mediated decrease of aortic regurgitation.

The effect of captopril mediated afterload reduction on aortic regurgitation was investigated in 10 patients. Regurgitation was quantitated by means of the regurgitation fraction and the relation of regurgitant volume to end diastolic volume. These variables were derived from gated radionuclide ventriculography. After captopril treatment the blood concentration of angiotensin I rose whereas that of angiotensin II fell significantly. The conversion of angiotensin I to II was reduced to about 50% of the control value. Whereas blood pressure and heart rate did not change significantly, the regurgitation fraction and the regurgitant volume, normalised to end diastolic volume, were significantly reduced by captopril treatment. The ejection fraction remained essentially unchanged. These findings suggest that captopril reduces aortic regurgitation by reducing afterload.

[Reduction of regurgitation in aortic insufficiency by inhibition of the renin-angiotensin converting enzyme]. / Reduktion der Regurgitation bei Aorteninsuffizienz durch Hemmung des Renin-Angiotensin-Konversionsenzyms.

The effect of captopril-mediated afterload reduction on regurgitation was investigated in 10 patients with aortic insufficiency. Regurgitation was quantitated by the regurgitation fraction and the relation of regurgitant volume to enddiastolic volume, which were derived from gated radionuclide ventriculography. 19 patients with coronary artery disease and no evidence of valvular heart disease served as controls. In patients with coronary artery disease no significant regurgitation was found. In patients with aortic regurgitation the blood concentration of angiotensin I increased whereas that of angiotensin II decreased significantly after captopril-medication; thus, the conversion of angiotensin I to II was reduced to about 50% of the control value. Whereas blood pressure and heart rate did not change significantly, the regurgitation fraction and the normalized regurgitant volume were significantly reduced. The ejection fraction remained essentially unchanged. These findings suggest a favorable influence of captopril-induced afterload reduction on hemodynamics in aortic regurgitation.

[Pulsed Doppler echocardiography in aortic valve disease]. / Gepulste Doppler-Echokardiographie bei Aortenvitien.

The diagnostic value of pulsed Doppler echocardiography (PDE) had not been sufficiently assessed up until now. Invasive catheter velocitometric measurements in the central vessels give quantitative information on the blood movement across the aortic and pulmonary valves. It is particularly useful in the quantification of aortic regurgitation. We successfully investigated 52 patients by means of PDE (ATL 500 A); 20 were suffering pure aortic incompetence, 11 pure stenosis and 21 had combined stenosis and regurgitation. Fifteen patients without aortic valvular disease served as controls. Our findings were compared with the results of cardiac catheterization and angiography in each case. In addition, 14 patients with aortic regurgitation were studied invasively by catheter velocitometry. The obtained regurgitation values were compared to the PDE method. In the PDE the underlying criteria for the assessment of the recordings were as follows: formal analysis of the analog signal and of the turbulence content during systole and diastole; in the flow velocity tracings aortic incompetence showed a steep increase with high peak to peak aortic velocities and scant turbulence formation; the reverse flow during regurgitation was accompanied by a high grade turbulent velocity pattern. The area under the diastolic (regurgitant) flow velocity curve (the time-amplitude integral) corresponded significantly with the angiographic severity of aortic insufficiency (r = 0.87). In aortic stenosis, turbulence formation leads to an approximately flat velocity profile across the ascending aorta, if the region in the vicinity of the valve is omitted. The flow velocity analog signals are considerably disturbed. However, the turbulence content which can be qualitatively estimated from the recordings, correlates well with the calculated valve area. In combined aortic valve stenosis and incompetence, the prevailing turbulent pattern does not always permit one to assess sufficiently the severity of the stenotic component, whereas the grade of incompetence can be, in general, evaluated. PDE complements the existing non-invasive techniques and probably essentially enriches non-invasive diagnostics.

Klinefelter's syndrome and mitral valve prolapse. an echocardiographic study in twenty-two patients.

It is well known that the incidence of mitral valve prolapse is increased in various hereditary and humoral disorders, particularly in diseases with abnormal collagene structure and metabolism. We consecutively investigated, both clinically and echocardiographically, 22 patients with Klinefelter's syndrome (Mean age: 35 +/- 15.8 years). On clinical examination one third (7 patients) showed clinical signs of connective tissue weakness, 9 patients were obese. In 3 patients without a history of rheumatic fever mitral regurgitation was present. A mid-systolic click was heard in 12 patients, in 8 of them a click-murmur syndrome. Mitral regurgitation has been found in 3 patients. Echocardiographic ally, 12 of 22 patients (55%) revealed mitral valve prolapse which was not correlated with the degree of the chromosomal aberration. The incidence of mitral valve prolapse in an otherwise healthy male population is reported to be approximately 6%. Thus, in Klinefelter's syndrome, the frequency of mitral valve prolapse is found to be markedly increased. Regarding the nosological implications of mitral valve prolapse, it is recommended to thoroughly examine patients cardiologically. Furthermore, since mitral valve prolapse bears a higher risk of malignant cardiac arrhythmias, chest pain and endocarditis, an antiarrhythmic treatment and--if indicated--antibiotic prophylaxis has to be instituted. Those patients also should be advised to adjust their life style appropriately.

[Clinical aspect and noninvasive diagnosis of cardiac myxomas]. / Klinik und nichtinvasive Diagnostik von kardialen Myxomen.

The alteration of cardiac function in the presence of intracardiac tumors varies considerably according to their localization, size, and mode of insertion. Various cardiovascular diseases can be mimicked, e.g., primary valve dysfunction, cardiomyopathy, intracardiac shunts. Embolic events are frequent secondary symptoms. However, subtle noninvasive techniques such as M-mode and sector echocardiography, pulsed Doppler echocardiography, digital video subtraction angiography (DVSA), and computed tomography permit a thorough diagnosis of intracardiac tumorous masses without heart catheterization and catheter angiography. In this paper, myxomas within the left atrium (LA) and the right ventricle (RV) are described. Leading symptoms were systemic embolism and mitral stenosis (LA localization), low cardiac output and right to left shunt (RV localization). First suspicion of intracardiac tumor was raised by M-mode and sector echocardiography, whereas the diagnosis of LA myxoma was in one case missed by computed tomography and the RV myxoma was missed by right ventricular catheterization. In that case, only the four-chamber subxiphoidal sector echogram substantiated the diagnosis and explained the hemodynamic constellation of very low pulmonary pressures combined with right to left shunt. By the new technique of DVSA, all three tumors were plainly visualized. Nevertheless, echocardiography proved to be the most reliable technique of detecting intracardiac tumors.

[Pulsed Doppler-echocardiographic study of mitral valve dysfunction]. / Gepulste Doppler-Echokardiographie bei Mitralvitien.

67 patients (pts)--20 with intact cardiac valve function, 15 with pure mitral stenosis, 20 with both mitral valve insufficiency and stenosis, 12 pts with pure mitral incompetence - have been investigated by non-invasive pulsed Doppler-echocardiography (PDE) previous to invasive right and left heart catheterization. The following criteria for evaluation of the PDE registrations are adopted: 1) Time-related correlation of ECG and flow velocity. 2) Formal analysis of the flow-velocity tracings. 3) Turbulence formation. 4) Maximum duration of flow. In pure mitral insufficiency, systolic turbulence formation is detected within the left atrium, which is present according to the severity only locally or throughout the entire left atrium. We calculated a specificity for the diagnosis of mitral incompetence of 94% and a sensitivity of 78%. In mitral stenosis a severity-dependent ventricular inflow velocity is prevalent - with an insidious onset until a dome-like or saw-tooth-like profile. Grading for severity of mitral stenosis can be performed as follows: the time from onset to maximum flow velocity of the diastolic inflows is measured and related to the time period of the cardiac cycle. A specificity of PDE for mitral stenosis of 88% and a sensitivity of 91% have been found. PDE is also being applied for assessment of hemodynamic efficacy of prosthetic mitral-valve replacement. In the evaluation of mitral valve dysfunction, PDE as a non-invasive technique is of high specificity and sensitivity as compared with the hemodynamic results of invasive procedures.

[Do fixed combinations of digoxin and nitrates have a therapeutic advantage?]. / Bringen fixe Kombinationen von Digoxin und Nitraten einen therapeutischen Vorteil?

The results of this study with 102 patients, suffering from cardiac insufficiency and coronary heart disease are that a fixed combination of digoxin with nitrate-compositions is not convenient. In 45 cases the digoxin dose had to be altered, partly even several times, whilst only in 23 patients an alteration of the dosage of the nitrate compositions had to be done, independently from the digoxin dose.