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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.

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.

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.

In this approach, we modeled somatostatin receptor-ligand complexes. Based on the information obtained from the structures of the ligand-receptor complexes, we designed and synthesized novel somatostatin analogs with enhanced selectivities.

We report the conformational analysis by 1H nmr in DMSO and computer simulations involving distance geometry and molecular dynamics simulations of analogs of the cyclic octapeptide D-Phe1-c[Cys2-Phe3-D-Trp4-Lys5-Thr6-Cys 7]-Thr8-ol (sandostatin, octreotide). The analogs D-Phe1-c[Cys2-Phe3-D-Trp4-Lys5-Xaa6-Cys 7]-Xbb8-NH2 (Xaa = allo-Thr, D-allo-Thr, D-beta-Hyv, beta-Hyv, D-Thr, and Xbb = Thr or Xaa = Thr and Xbb = allo-Thr, D-allo-Thr, beta-Hyv, D-Thr) contain stereochemical changes in the Thr residues in positions 6 and 8, which allow us to investigate the influence of the stereochemistry within these residues on conformation and binding affinity. The molecular dynamics simulations provide insight into the conformational flexibility of these analogs. The compounds with (S)-configuration at the C(alpha) of residue 6 adopt beta-sheet structures containing a type II' beta-turn with D-Trp in the i+1 position, and these conformations are "folded" about residues 6 and 3. The structures are very similar to those observed for sandostatin, and the disulfide bridge results in a close proximity of the H(alpha) protons of residues 7 and 2, which confirms earlier observations that a disulfide bridge is a good mimic for a cis peptide bond. The compounds with (R)-configuration at the C(alpha) of residue 6 adopt considerably different backbone conformations. The structures observed for these analogs contain either a beta-turn about residue Lys and Xaa6 or a gamma-turn about the Xaa6 residue. These compounds do not exhibit significant binding to the somatostatin receptors, while the compounds with (S) configuration in position 6 bind potently to the sst2, 3, and 5 receptors. The nmr spectra of analogs with (R) or (S) configuration at the C(alpha) of residue 8 are strikingly similar to each other. We have demonstrated that the chemical shifts of protons of residues 3, 4, 5, and 6, which are part of the type II' beta-turn, and especially the effect on the Lys gamma-protons are considerably different in active molecules as compared to inactive analogs. Since the presence of a type II' beta-turn is crucial for the binding to the receptors, the chemical shifts, the amide temperature coefficients of the Thr residue and the medium strength NOE between LysNH and ThrNH can be extremely useful as an initial screening tool to separate the active molecules from inactive analogs.

In a continuation of our research efforts on the design and synthesis of novel peptidomimetic structures, we have synthesized a series of sandostatin amide analogs in which stereoisomers of threonine and beta-hydroxyvaline(beta-Hyv) are employed. The analogs D-Phe1-c[Cys2-Phe3-D-Trp4-Lys5-Xaa6-Cys 7]-Xbb8-NH2 (Xaa = allo-Thr, D-allo-Thr, D-beta-Hyv, beta-Hyv, D-Thr, and Xbb = Thr or Xaa = Thr and Xbb = allo-Thr, D-allo-Thr, beta-Hyv, D-Thr) explore the effects on biological activity of stereochemical modifications and beta-methylation at positions 6 or 8. By these modifications, we examine the role of the two residues in binding to somatostatin receptors. We describe the synthesis and biological activity of these analogs. In combination with the results of the conformational analysis, this study provides new insights into the structural requirements for the binding affinity of somatostatin amide analogs to somatostatin receptors [Mattern et al., Conformational analyses of sandostatin analogs containing stereochemical changes in positions 6 or 8].

This paper reports a detailed conformational characterization in solution by 1H-NMR in H2O and DMSO-d6 and molecular modeling simulations of cyclic peptides containing the RGDDV pharmacophore and the RGDY(Me)R pharmacophore. These two pentapeptide sequences when properly constrained in cyclic peptides are low to sub-nanomolar inhibitors of integrin alpha(v)beta3. The peptides containing the RGDDY(Me)R sequence bind potently to integrin alphaIIb3 as well. The conformations found in H2O and in DMSO-d6 solutions are valuable for the design of peptidomimetics of these two pharmacophores. The structure-activity relationships of the RGDDV and RGDY(Me)R pharmacophores within cyclic peptides are discussed. Specifically, the orientation of surface-accessible chemical features on the ligand, such as hydrophobic, positive and negative ionizable groups, which are considered to be responsible for the desired biological activity, is focused on.

We report the synthesis, binding affinities to the recombinant human somatostatin receptors, and structure-activity relationship studies of compounds related to the cyclic hexapeptide, c-[Pro6-Phe7-D-Trp8Lys9-Thr10-Phe11], L-363,301 (the numbering in the sequence refers to the position of the residues in native somatostatin). The Pro residue in this compound is replaced with the arylalkyl peptoid residues Nphe (N-benzylglycine), (S)betaMeNphe [(S)-N-[alpha(-methyl)benzyl]glycine] or (R)betaMeNphe [(R)-N-[(alpha-methyl)benzyl]glycine] and L-1-naphthylalanine is incorporated into either position 7 or 11 of the parent compound. The synthesis and binding data of the Nnal6 ([N-naphthylmethyl]glycine) analog of L-363,301 is also reported. The incorporation of the Nnal residue into position 6 of L-363,301 resulted in an analog with weaker binding affinities to all hsst receptors but enhanced selectivity towards the hsst2 receptor compared with the parent compound. The other compounds bind effectively to the hsst2 receptor but show some variations in the binding to the hsst3 and hsst5 receptors resulting in different ratios of binding affinities to the hsst5 and hsst2 or hsst3 and hsst2, respectively. The incorporation of the Nphe residue into position 6 and the Nal residue into position 7 of L-363,301 led to a compound which binds potently to the hsst2 and has increased selectivity towards this receptor (weaker binding to hsst3 and hsst5 receptors) compared with the parent compound. The analogs with beta-methyl chiral substitutions in the aromatic peptoid side chain and Nal in position 7 or 11 bind effectively to the hsst2 and hsst5 receptors. They exhibit similar ratios of binding affinities to the hsst5 and hsst2 receptors as observed for L-363,301. There are however minor differences in binding to the hsst3 receptor among these analogs. These studies allow us to investigate the influence of additional hydrophobic groups on the binding activity to the isolated human somatostatin receptors and the results are important for the design of other somatostatin analogs.

We report the conformational analysis by 1H-NMR in DMSO and computer simulations involving distance geometry and molecular dynamics simulations of peptoid analogs of the cyclic hexapeptide c-[Phe11-Pro6-Phe7-D-Trp8-Lys9-Thr10] L-363,301 (the numbering refers to the positions in native somatostatin). The compounds c-[Phe11-Nphe6-Nal7-D-Trp8-Lys9-Thr10] (Nphe6-Nal7 analog 1), c-[Nal11-Nphe6-Phe7-D-Trp8-Lys9-Thr10] (Nal11-Nphe6 analog 2) and c-[Phe11-Nnal6-Phe7-D-Trp8-Lys9-Thr10] (Nnal6 analog 3), where Nphe denotes N-benzylglycine and Nnal denotes N-(1-naphthylmethyl)glycine, are subjected to SAR studies in order to investigate the influence of the bulky naphthyl aromatic ring on the conformation. The Nal11-Nphe6 and Nphe6-Nal7 analogs exhibit potent binding to the hsst2, hsst3 and hsst5 receptors, whereas the Nnal6 analog has decreased binding affinity to all receptors but is more selective towards the hsst2 than the other two analogs and L-363,301. The conformational search employing distance geometry, energy minimization and molecular dynamic simulations gives insight into the conformational flexibility of these analogs. The molecules adopt both cis and trans orientations of the peptide bond between residues 11 and 6. The cis isomers of these analogs adopt type II' beta-turns with D-Trp in the i + 1 position and type VIalpha beta-turns with the cis peptide bond between residues 6 and 11. The results of free and distance restrained molecular dynamics simulations at 300 K indicate that the Nphe6-Nal7 and Nal11-Nphe6 compounds adopt a preferred backbone conformation which can be described as 'folded' about residues 7 and 10. The Nnal6 analog, which binds less effectively to the hsst receptors, has a more flexible backbone structure than the Nal11-Nphe6 and Nphe6-Nal7 analogs and prefers a 'flat' structure with regard to the orientations about Phe7 and Thr10 during molecular dynamics simulations.

We report the conformational analysis by 1H NMR in DMSO and computer simulations involving distance geometry and molecular dynamics simulations at 300K of peptoid analogs of the cyclic hexapeptide c-[Phe11-Pro6-Phe7-D-Trp8-Lys9-Thr10]. The analogs c-[Phe11-Nasp6-Phe7-D-Trp8-Lys9-Thr10](1), c-[Phe11-Ndab6Phe7-D-Trp8-Lys9-Thr10] (2) and c-[Phen11-Nlys6-Phe7-D-Trp8-Lys9-Thr10](3) where Nasp denotes N-(2-carboxyethyl) glycine, Ndab N-(2-aminoethyl) glycine and Nlys N-(4-aminobutyl) glycine are subject to conformational studies. The results of free and restrained molecular dynamics simulations at 300K are reported and give insight into the conformational behaviour of these analogs. The compounds show two sets of nuclear magnetic resonance signals corresponding to the cis and trans orientations of the peptide bond between residues 11 and 6. The backbone conformation of the cis isomers that we believe are the bioactive isomers of the three compounds are very similar to each other while there are larger variations amongst the trans isomers. The binding data to the isolated receptors show that the introduction of the Nlys residue in analog 3 leads to an enhancement of binding potency to the hsst5 receptor compared with analog 2 while maintaining identical binding potency to the hsst2 receptor. The Nasp6 analog 1 binds weakly to the hsst2 and is essentially inactive towards the other receptors. Comparison of the conformations and binding activities of these three analogs indicates that the Nlys residue extends sufficiently far to allow binding to a negatively charged binding domain on the hsst5 receptor. According to this model, the Ndab analog 2 cannot extend far enough to allow for binding to the receptor pocket. The loss of activity observed for the Nasp6 compound 1 indicates that the presence of a negatively charged residue in position 6 is unfavorable for binding to the hsst receptors.

The synthesis, binding affinity, and structure-activity relationships of compounds related to the cyclic hexapeptide, c[Pro6-Phe7-D-Trp8-Lys9-Thr10-Phe11], L-363,301 (the numbering in the sequence refers to the position of the residue in native somatostatin) is reported. The Pro residue in this compound is replaced with the peptoid residues Nasp [N-(2-carboxyethyl) glycine], Ndab [N-(2-aminoethyl) glycine] and Nlys [N-(4-aminobutyl) glycine]. This series of compounds enables us to draw conclusions about the influence of positively or negatively charged residues in the bridging region on the binding affinity towards the isolated human somatostatin receptors. A loss of binding to the recombinant human somatostatin (hsst) receptors in the Nasp analog compared with L-363,301 and compared with the Ndab and Nlys analogs clearly demonstrates that the presence of an acidic residue in the bridging region is unfavorable for binding to the hsst receptors. Comparison between the Ndab analog and the Nlys analog suggests that the presence of a basic residue in the bridging region might be advantageous for binding to the hsst5 receptor provided that the residue bearing the basic group extends far enough to allow for interaction with the receptor, while the length of the basic peptoid residue does not influence binding to the hsst2 receptor. These results are useful for the design of hsst5 selective somatostatin analogs.

The molecular basis of sweet taste was investigated by carrying out the crystal state conformational analysis by X-ray diffraction of the following dipeptide taste ligands: N-3,3-dimethylbutyl-aspartylphenylalanine methyl ester, I (N-DMB-Asp-Phe-OMe), its sodium salt (N-DMB-Asp-Phe-ONa), II, aspartyl-D-2-aminobutyric acid-(S)-alpha-ethylbenzylamide, III (Asp-D-Abu-(S)-alpha-ethylbenzylamide), aspartyl-N'-((2,2,5,5-tetramethylcyclopentanyl)-carbonyl)-(R)- 1,1-diamino-ethane, IV (Asp-(R)-gAla-TMCP), and aspartyl-D-valine-(R)-alpha-methoxymethylbenzyl amide, V (Asp-D-Val-(R)-alpha-methoxymethylbenzylamide). With the exception of the sodium salt II, all compounds are sweet-tasting, showing in some cases considerable potency enhancement with respect to sucrose. The results of this study confirm the earlier model that an 'L-shape' molecular array is essential for eliciting sweet taste for dipeptide-like ligands. In addition, it was established that (i) substitution of the N-terminal group does not inhibit sweet taste, if its zwitterionic character is maintained; (ii) a hydrophobic group located between the stem and the base of the L-shape could be responsible for sweetness potency enhancement, as found in I, III and IV; in fact, the extraordinary potency of the N-alkylated analogue I would support a model with an additional hydrophobic binding domain above the base of the 'L'; (iii) removal of the methyl ester at the C-terminus of compound I with the salt formation gives rise to the tasteless compound II; (iv) for the first time all possible side-chain conformers (g-, g+ and t) for the N-substituted aspartyl residue were observed; and (v) a retro-inverso modification, incorporated at position 2 of the dipeptide chain, confers greater flexibility to the molecule, as demonstrated by the contemporary presence of six conformationally distinct independent molecules in the unit cell and yet sweet taste properties are maintained, as found in IV.

Fast jeder zweite Patient mit systemischem Lupus erythematodes entwickelt eine Mitbeteiligung des Herzens. Meistens handelt es sich dabei aber zum Gluck nur um leichte Veranderungen. Betroffen sein konnen Herzmuskel, Herzbeutel, Herzkranzgefase und auch das „Nervensystem“ des Herzens.

ZusammenfassungBei 10 Patienten mit Aorteninsuffizienz wurde der Einfluß der Nachlastsenkung durch Captopril-induzierte Hemmung des Angiotensin-Konversionsenzyms auf die Regurgitation untersucht. Als Maß für die Regurgitation diente die Regurgitationsfraktion und das Verhältnis des regurgitierten Volumens zum enddiastolischen Volumen; diese Parameter wurden mit Hilfe der Radionuklid-Ventrikulographie ermittelt. 19 Patienten mit koronarer Herzerkrankung ohne Herzklappenerkrankung dienten als Kontrollen. Bei Patienten ohne Klappenvitium wurde keine signifikante Regurgitation festgestellt. Bei Patienten mit Aorteninsuffizienz bewirkte Captopril eine signifikante Zunahme der Angiotensin I- und Abnahme der Angiotensin II-Konzentration im Blut; die daraus errechnete Konversionsrate von Angiotensin I und II nahm um 50% ab. Blutdruck und Pulsfrequenz wurden durch Captopril nicht signifikant beeinflußt. Im Gegensatz dazu fand sich eine signifikante Abnahme der Regurgitationsfraktion und des auf das enddiastolische Volumen normierten Regurgitationsvolumens; die Auswurffraktion wurde durch Captopril nicht signifikant verändert. Diese Befunde weisen auf eine Ökonomisierung der Herzarbeit bei Aorteninsuffizienz durch Captopril-induzierte Nachlast-Senkung hin.

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.

Diffuse pulmonary fibroleiomyomas were detected by open-lung biopsy in a 33-year-old male patient. Lung function studies revealed severe airflow obstruction, hyperinflation, grossly impaired single-breath-diffusing capacity and a decrease in PaO2 during exercise, i.e. data which are compatible with pulmonary emphysema. However, static lung compliance was within normal limits excluding the existence of pure emphysema. Additional special lung function tests confirmed the assumption that in diffuse fibroleiomyomas of the lung, functional patterns characteristic of obstructive and restrictive lung disease are present that are in agreement with the histological features of this disease.

Bericht uber einen 40jahrigen Patienten, der seit 5 Jahren an einer progredienten Myopathie litt und neurologisch das Bild einer atypischen Beckengurteldystrophie bot. Im EMG wurden myotone und pseudomyotone Entladungen beobachtet. Die enzymhistochemischen und elektronenoptischen Untersuchungen der Muskelbiopsien und eines Leberpunktates wiesen auf eine Glykogenose hin; die biochemische Untersuchung bestatigte den Mangel an saurer Maltase. Weitere Literaturfalle von Saure-Maltase-Mangel-Syndrom im juvenilen und Erwachsenenalter wurden uberpruft. Es stellt sich heraus, das mit zunehmendem Alter des Patienten ein fast selektiver Befall der proximalen Muskeln auftritt, was oft Anlas zur Verwechslung mit anderen sog. degenerativen neuromuskularen Erkrankungen gibt. Bioptische und biochemische Untersuchungen sind daher in solchen Fallen besonders indiziert. Der langsamere Verlauf dieser generalisierten Speicherkrankheit im Erwachsenenalter — gegenuber der rasch verlaufenden infantilen Form (Pompesche Erkrankung) — bleibt ungeklart.

In atrial fibrillation an optimal frequency value has been derived to give the maximum cardiac output. A multiple, non-linear regression analysis of phasic aortic flow velocity in 12 patients with atrial fibrillation yields the parameters: (i) upper limiting frequency, f c ; and (ii) ‘optimal’ frequency of the heart f o = f c /2. f o is defined at maximum cardiac output in resting conditions. An estimate of f c may be obtained from the carotid pulse tracing in a non-invasive way for the individual patient. The maximum cardiac output at f o ranges between 100% and 125% of the cardiac output was measured in the atrial fibrillatory state with irregular excitation of the ventricles. The greater the degree of irregularity of atrial fibrillation, the more expressed was the potential rise in cardiac output at the optimal regularization frequency. In chronic atrial fibrillation a regular excitation of the ventricles could be achieved by pharmacological agents, such as Verapamil or by ventricular pacing, without restitution of normal sinus rhythm. In critically ill patients with atrial fibrillation and the low cardiac output syndrome the heart rate should be adjusted to the individual cardiac output-related optimal frequency.

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. Differencies 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.

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.

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.

The article reports on a case of hydrops fetalis caused by Kell antibodies, antibody formation having been triggered by pregnancy. Since the relative frequency of Kell (and rhesus sub-group) intolerance is increasing due to the successes achieved by anti-D-immunoglobulin prophylaxis, the question arises, on account of the possibly severe course of the disease, whether the Kell factor should be taken into consideration in all blood transfusions in girls during their childhood and in women of childbearing age.

Bei 40 Patienten mit Aorten (AS, AI) — bzw. Mitralvitien (MS, MI), sowie Mitralklappenprolaps (MKP) wurden die Stromungsgeschwindigkeit (u) und die Blutbeschleunigung (u) in der Aorta asc. quantitativ mit einem Katheterspitzeninstrument gemessen. Die umax in der Aorta des Menschen schwankt in Ruhe zwischen 32 und 190 cm/s, die umax zwischen 0.8 und 7.2 g (1 g = 981 cm/s2).

The article reports on a case of hydrops fetalis caused by Kell antibodies, antibody formation having been triggered by pregnancy. Since the relative frequency of Kell (and rhesus sub-group) intolerance is increasing due to the successes achieved by anti-D-immunoglobulin prophylaxis, the question arises, on account of the possibly severe course of the disease, whether the Kell factor should be taken into consideration in all blood transfusions in girls during their childhood and in women of childbearing age.

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.

31 patients (Pt) with Mitral Valve Repacement (MVR), 22 Pt with Aortic VR (AVR) and 10 Pt with Double VR (DVR) are investigated hemodynamically and by ergometry. Normal working capacity (100% WC) has been achieved in 59% of Pt with AVR, in 34% with MVR and in 22% with DVR. Pulmonary artery mean pressure (PAMP) in this group was 19.5 mmHg, in a second group with a WC of 80% PAMP was 22.2 mmHG. 77% OF Pt with AVR are working regularly, in MVR 58% and in DVR 50%. In the average of these Pt, 7 months after VR professional occupation is started again. PAMP and pulmonary vascular resistance (APR) is significantly lower in the working vs. the non working group: PAMP 19.8/23.7 mmHg; APR 115/145 dynes sec cm-5, respectively. In MVR, the transprosthetic pressure gradient at rest was 4.1 (working PPT) and 7.5 mmHg (other); in AVR statistically no significant difference in the gradient could be found. In general, 68% of the working Pt are employed in a preferably sedentary job. The mean duration of daily work was estimated to 6.7 hours. It is concluded that AVR yields more favourable results in terms of regaining normal working activity than MVR. Cardiovascular function and physical capability in Pt with DVR are approximately comparable to MVR.

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.

In patients with mitral valve replacement an acute cardiac decompensation most often signalizes malfunction of the prosthesis. Echocardiography proves to be of great value in the noninvasive diagnostic to detecting valve dysfunction. The echocardiogram of two patients few weeks after cardiac surgery was strongly suggestive of perivalve leak with severe regurgitation: enlarged left atrium and left ventricle, hyperactive septal motion and hyperkinetic motion of the left ventricular posterior wall, unique "hump" in early diastole with normal excursion, opening and closing velocity of the disc. The echocardiogram of one patient exhibited the pattern of mitral stenosis: large left atrium, decreased amplitude of excursion of the opening of the disc with a slowing and "rounded" opening upstroke as well as a slowed and "rounded" downstroke with prolonged opening and closing rates of the disc. One patient with aortic and mitral valve replacement showed no echocardiographic signs of abnormal disc motion. The reason for the cardiac decompensation was an acute malfunction of the left ventricle. The echocardiographic findings were confirmed by cardiac catheterization, left ventricular cineangiography or direct inspection during open heart surgery.

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.