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Biomedical subjects

A Neumann

Publications and source records attributed to A Neumann.

At least 91 records · Page 5Linked to original sources

Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies.

Homozygous protein C deficiency or homozygous protein S deficiency are rare genetic diseases with catastrophic and fatal purpura fulminans-like or thrombotic complications occurring during the neonatal period. These diseases can now be successfully treated. Purpura fulminans is at least in part a cutaneous manifestation of the syndrome of systemic DIC. It is characterized by microvascular thrombosis in the dermis followed by perivascular hemorrhage, necrosis, and minimal inflammation. Laboratory findings are consistent with DIC. Although the pathogenesis is not fully understood, the DIC in purpura fulminans appears to involve the skin selectively. The development of purpura fulminans from homozygous protein C or protein S deficiencies can be separated into the two distinct phases. The first phase is the time period when the initial reversible lesions develop and grow. This reversible progression can be halted and reversed with the administration of protein C or protein S. The second phase is the irreversible stage in which the lesion continues to develop into a necrotic lesion, whether or not treated with protein C. This irreversible lesion will ultimately develop into a large full-thickness necrotic injury of the skin. It is very similar to the lesions seen in idiopathic purpura fulminans, warfarin-induced skin necrosis, and acute infectious purpura fulminans. Unfortunately, our current understanding of the mechanism or mechanisms of the induction and propagation of the purpura fulminans-like lesions in homozygous protein C or protein S deficiencies is minimal, since it has never been studied. We can only speculate on the mechanism based on laboratory data and comparison with the little that is known about the other similar types of lesions.

Glycoproteins↗

[Arthroscopic cruciate ligament reinsertion and augmentation. Indications--surgical technic].

The advantages of arthroscopic refixation and augmentation of the cruciate ligament in comparison to open methods are conserving innervation of the most important structures of the knee joint, a clear-cut reduction in morbidity, and more rapid rehabilitation of the knee joint. In principle, however, as far as ligament replacement and fixation of the augmented ligament parts are concerned, the technique corresponds to the open method. As the early results refer to a period of 2 years at most, however, it is too soon to report them. Nevertheless, the results of follow-up in our present study are identical to those previously reported by other authors.

Arthroscopes↗

Comparison of Doppler indexes of left ventricular diastolic function with simultaneous high fidelity left atrial and ventricular pressures in idiopathic dilated cardiomyopathy.

Doppler echocardiographic indexes of ventricular inflow have been used clinically to characterize left ventricular (LV) diastolic function. The reliability of these indexes as markers for intrinsic myocardial diastolic properties has been questioned. Micro-manometer left atrial (LA) and LV pressures as well as transmitral Doppler flow velocity signals and M-mode and 2-dimensional echocardiograms were simultaneously recorded. These unique measurements were acquired in patients with dilated cardiomyopathy under baseline conditions and during infusion of high dose amrinone. The response to amrinone was chosen as a hemodynamic model because this drug has previously been described as having beneficial effects on overall LV systolic and diastolic performance. At peak amrinone effect, LV contractility increased (as assessed using load independent end-systolic indexes) and early diastolic relaxation improved whereas passive chamber stiffness, heart rate and stroke volume were unchanged. There was a significant decrease in LV end-diastolic pressure as well as a parallel downward shift of the entire LV diastolic pressure-dimension relation. These findings, which indicated an improvement in overall LV diastolic properties, probably represent the combination of more rapid early diastolic relaxation in conjunction with a reduction in venous return, the relief of pericardial restraint or the reduction in right ventricular-LV interaction. In contrast, the ratios of Doppler-determined peak transmitral early-to-late flow velocities and early-to-late diastolic flow velocity integrals decreased with amrinone infusion, thereby suggesting a drug-induced decrease in LV diastolic compliance. Thus, in patients with idiopathic dilated cardiomyopathy, administration of amrinone has a complex effect on LV diastolic properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cardiac and peripheral vascular responses to adrenoceptor stimulation and blockade after cardiac transplantation.

A denervated heart coupled to a periphery previously exposed to high catecholamine levels provides a unique model to study adrenoceptor physiology. Six orthotopic transplant patients (1.3 +/- 0.8 years postoperative) were age matched with six atropine-treated normal subjects. Simultaneous two-dimensionally targeted left ventricular echo-cardiograms and calibrated carotid pulse tracings were recorded. Left ventricular contractility was assessed with use of heart rate- and load-independent end-systolic indexes. Studies were performed at baseline and during dobutamine infusion with and without beta-adrenergic blockade with use of propranolol; effects were assessed during afterload changes generated by the alpha 1 agonist methoxamine. There were no differences in baseline contractility or reserve between transplant patients and normal subjects. The heart rate response to dobutamine was greater for transplant patients (p less than 0.001). In both groups, the positive inotropic and chronotropic effects of dobutamine were ablated by propranolol. Dobutamine plus propranolol (unopposed alpha 1 effect) did not change mean systemic pressure in transplant patients while markedly raising mean systemic pressures in normal subjects (36 +/- 18 mm Hg; p less than 0.001). In addition, during initial challenge with methoxamine, the transplant patients required 60% more alpha 1 agonist than did the normal subjects (p less than 0.001) to obtain a pressor effect. In summary, transplant patients who were previously in severe heart failure have normal left ventricular inotropic response to beta 1 activation and blockade, exaggerated chronotropic response to dobutamine and reduced sensitivity to stimulation with alpha 1-adrenoceptor agonists. These findings are consistent with a differential response of adrenoceptors to long-term stimulation after cardiac transplantation.

Adult↗

Frequencies of Borrelia burgdorferi-reactive T lymphocytes in Lyme arthritis.

Using a limiting dilution system, frequencies of Borrelia burgdorferi-reactive T cells were determined in the blood and synovial fluid of four patients with chronic Lyme arthritis (LA), one patient with acrodermatitis chronica atrophicans (ACA), two patients with other inflammatory joint diseases, and two healthy individuals. B. burgdorferi-reactive precursor T cells ranged from 1/750 to 1/8220 in case of LA and ACA patients and from 1/820 to 1/31 400 in case of controls. In vivo activated B. burgdorferi-reactive T cells were almost absent in control subjects. With one exception, they were detected in LA patients at frequencies ranging from 1/1 300 to 1/15 400. Interestingly, even after successful antibiotic therapy of LA patients, similar frequencies of in vivo activated B. burgdorferi-reactive T cells were observed in the peripheral blood, provided that low cell concentrations were used for culture. At higher cell numbers, the fraction of B. burgdorferi-reactive T cells apparently dropped, suggesting regulatory phenomena.

Adult↗

Physiological mechanisms for calcium-induced changes in systemic arterial pressure in stable dialysis patients.

The mechanisms by which variations in blood ionized calcium (Ca2+) influence systemic arterial pressures independent of changes in extracellular fluid volume, pH, and electrolytes are unknown. To study this issue, we dialyzed eight stable hemodialysis patients on three separate occasions during 1 week with dialysates differing only in calcium concentration. Ultrafiltration was adjusted to achieve the patient's estimated dry weight. Postdialysis Ca2+ was measured, as were arterial blood gases, electrolytes, magnesium, blood urea nitrogen, creatinine, and hematocrit. Blood pressures and two-dimensional, targeted M-mode echocardiograms were recorded with the patient in the supine position after 15 minutes of rest. Postdialysis, three different levels of Ca2+ were achieved. Other measured biochemical variables and body weight did not differ among the three study periods. Changes in Ca2+ correlated directly with changes in systolic, diastolic, and mean blood pressures, left ventricular stroke volume, and cardiac output. In contrast, heart rate, left ventricular end-diastolic dimension, and total systemic vascular resistance were not altered significantly by changes in Ca2+. Thus, alterations in Ca2+ within the physiological range affect systemic blood pressure primarily through changes in left ventricular output rather than in peripheral vascular tone in stable dialysis patients.

Adult↗

Contrast echocardiography: effects of microbubbles on coronary blood flow and left ventricular hemodynamics.

Contrast echocardiography is currently being used to define and quantitate myocardial perfusion at the time of cardiac catheterization. Limited and conflicting data exist regarding the physiologic effects of microbubble-containing contrast agents. In the present study, coronary blood flow measured using an electromagnetic flow meter, blood pressure, and heart rate responses were studied in six dogs. An ECG-gated power injector was used to deliver 7 to 9 ml of sonicated and nonsonicated solutions (saline, Renografin-76, dextrose 50% and 70%, and sorbitol 70%) through an intra-aortic catheter placed above the aortic cusps. Paired injections of sonicated and nonsonicated agents were compared to determine whether the presence of microbubbles affected the physiologic response to these agents. Simultaneous recordings of two-dimensional cross-sectional images of the left ventricle were obtained. Data are expressed as percentage of change from preinjection control values. Within 10 seconds of an injection, decreases in coronary blood flow occurred in a range from -1 to -10% compared with preinjection control values. Coronary blood flow increased between 10 and 25 seconds postinjection within a range from +11 to +29%. Systemic blood pressures rose during injections and then declined below control values within 10 seconds. The magnitude of the decline in systolic blood pressure ranged from -5. to -18%. Diastolic blood pressure declined in a range from -13 to -33%. Within 20-30 seconds postinjection, systemic blood pressure rose above control values. The magnitude of the systolic and diastolic blood pressure rise ranged from +4 to +11%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of the beta 2 adrenoceptor in mediating positive inotropic activity in the failing heart and its relation to the hemodynamic actions of dopexamine hydrochloride.

In patients with severe congestive heart failure, it has been suggested that since myocardial beta 1 adrenoceptors are selectively down-regulated, activation of beta 2 receptors may be a preferable approach to augmenting contractility. Accordingly, dopexamine hydrochloride (1, 2 and 4 micrograms/kg/min) and dopamine (2 and 4 micrograms/kg/min) were administered to 8 patients with dilated cardiomyopathy. Left ventricular (LV) dimensions, thicknesses and pressures were obtained using simultaneous high-fidelity pressure measurements and echocardiographic recordings. LV contractility was assessed using the load-independent relation between LV end-systolic wall stress and rate-corrected velocity of fiber shortening. Cardiac index increased in a dose-related manner with both drugs, and was accompanied by a decline in systemic vascular resistance, a measure of peripheral arteriolar tone. LV end-diastolic pressure was unaltered except for a decrease from 29 +/- 6 to 19 +/- 5 mm Hg (p less than 0.017) at the highest dose of dopexamine hydrochloride. Heart rate was unchanged during the infusion of dopamine but increased significantly with dopexamine hydrochloride. LV end-systolic wall stress, a measure of LV internal load, decreased with both drugs. With dopamine, a dose-dependent positive inotropic effect was observed. Dopexamine hydrochloride, at the 4 micrograms/kg/min infusion dose, exerted a mild positive inotropic effect comparable to that noted with dopamine at 2 micrograms/kg/min. Thus, dopamine and dopexamine hydrochloride improved overall LV performance. With dopamine, a substantial positive inotropic effect occurred in association with a reduction in LV afterload. The increased cardiac index observed with dopexamine hydrochloride was due primarily to peripheral vasodilatation and a positive chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Contrast echocardiography during coronary arteriography in humans: perfusion and anatomic studies.

In humans, the physiologic relation between myocardial blood flow and epicardial coronary artery anatomy remains poorly defined. With the recent development of sonicated microbubble contrast agents, it is now possible to use contrast echocardiography to assess myocardial perfusion and to correlate blood flow with angiographically identified coronary artery anatomy. The purpose of the current study was to determine myocardial perfusion patterns in patients without significant coronary artery disease. The results may be used as a reference to analyze myocardial blood flow in patients with coronary artery disease. Sonicated meglumine sodium diatrizoate solution (Renografin-76), which contains microbubbles measuring 4.5 +/- 2.8 micrograms in diameter by laser analysis, was used as the echocardiographic contrast agent during elective coronary arterriography in 14 patients without significant coronary artery disease. Patients received intracoronary injections of 1.5 to 2 ml of sonicated Renografin-76 without complications. Perfusion characteristics were studied by visual assessment of the two-dimensional echocardiographic images obtained after individual injections. In patients found to be free of significant coronary artery disease by arteriography, the left coronary system always supplied the anteroseptal, anterior, anterolateral and posterior regions of the left ventricle at the mid-papillary, cross-sectional level. The right coronary artery system perfused the inferior and inferoseptal regions in 89% of the patients identified with a right dominant system. The anterolateral papillary muscle was perfused from the left coronary system in all cases. The posteromedial papillary muscle was perfused from the left coronary system in 58% of the patients and from the right system in 42% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Effects of dopamine on left ventricular afterload and contractile state in heart failure: relation to the activation of beta 1-adrenoceptors and dopamine receptors.

Although long-term therapy with oral beta-adrenoceptor agonists in patients with heart failure is generally associated with the development of diminished pharmacologic efficacy, the ingestion of levodopa, which is decarboxylated endogenously to dopamine, is associated with a sustained improvement in cardiac function. The beneficial hemodynamic actions of dopamine in patients with heart failure have been attributed to a positive inotropic effect that is mediated through activation of beta 1-adrenoceptors. However, a reduction in left ventricular afterload resulting from the activation of dopamine receptors may also lead to an improvement in the performance of the failing heart. To ascertain the relative importance of the positive inotropic and afterload-reducing effects of dopamine in patients with heart failure, dopamine (2, 4, 6 micrograms/kg per min), dobutamine (2, 6, 10 micrograms/kg per min) and nitroprusside (0.125 to 2.0 micrograms/kg per min) were administered to 13 patients with dilated cardiomyopathy while monitoring left ventricular wall thickness and dimensions by echocardiography and left ventricular and aortic pressures with a micromanometer-tipped catheter. Altering left ventricular afterload, quantified as end-systolic circumferential wall stress, with nitroprusside allowed generation of the left ventricular end-systolic circumferential wall stress-velocity of fiber shortening relation that represented the baseline contractile state of the myocardium. Left ventricular velocity of fiber shortening was elevated during the administration of dobutamine and dopamine when compared with measurements obtained with nitroprusside at the same left ventricular end-systolic circumferential wall stress. Furthermore, left ventricular end-systolic wall stress decreased with dopamine but not with dobutamine. Thus, the beta 1-adrenoceptor activity of dopamine and dobutamine augmented the contractile state of the myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Physiologic mechanisms governing hemodynamic responses to positive inotropic therapy in patients with dilated cardiomyopathy.

Clinical trials in patients with dilated cardiomyopathy (DCM) have shown a wide disparity in the hemodynamic responses to positive inotropic therapy. In addition, the response of the failing left ventricle to positive inotropic agents reflects the net interaction of multiple factors, including the magnitude of contractile abnormality and compensatory mechanisms. In the current study, left ventricular geometry, loading conditions, and contractile state were assessed in 13 patients with nonischemic DCM with the use of simultaneous high-fidelity pressure measurements and echocardiographic recordings. Comparisons were made with echocardiographic and calibrated carotid pulse data acquired in nine age-matched normal subjects. The patients with DCM were divided according to the left ventricular end-diastolic wall thickness-to-dimension ratio into groups with "appropriate" hypertrophy (i.e., less than or equal to 2 SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e., greater than 2 SDs from mean normal; n = 8; group 2). Age, New York Heart Association functional class, left ventricular wall mass index, and left ventricular end-diastolic pressure and dimension were similar for the DCM groups. Baseline left ventricular afterload (defined as circumferential end-systolic wall stress, sigma es) was 168% and 203% greater than normal in groups 1 and 2, respectively. The administration of the beta-adrenoceptor agonist dobutamine decreased left ventricular afterload by 12% in the normal subjects and by 10% in group 1 patients, while augmenting afterload by 5% in group 2 patients. The latter response occurred despite a 17% fall in systemic vascular resistance. Overall left ventricular performance, as assessed by the rate-corrected mean velocity of fiber shortening (Vcfc), was related to left ventricular afterload (i.e., sigma es). The resultant sigma es -Vcfc relationship, a sensitive measure of left ventricular contractility, was determined over a wide range of afterload conditions generated by methoxamine (normal subjects) or nitroprusside (DCM). Baseline left ventricular contractile state was 61% of normal for group 1 and 44% of normal for group 2. The contractile response to dobutamine infusion was 52% of normal for group 1 and only 22% of normal for group 2. Thus, positive inotropic therapy with dobutamine in patients with DCM is limited by (1) an attenuated contractile response and (2) elevated left ventricular afterload, which may be augmented further during its administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Dilated↗

Left ventricular contractility varies directly with blood ionized calcium.

STUDY OBJECTIVE: To determine the effect of variations in blood ionized calcium (Ca2+) on myocardial contractility independent of changes in loading conditions and other biochemical variables. DESIGN: Hemodialysis done in a randomized, double-blind manner with dialysates differing in calcium concentration only. Left ventricular contractility was assessed using the load- and heart rate-independent relationship between end-systolic wall stress (sigma es) and rate-corrected velocity of fiber shortening (Vcfc). SETTING: In-hospital dialysis unit and echocardiography laboratory of a university medical center. PATIENTS: Seven patients with stable, chronic renal failure maintained on regular hemodialysis. INTERVENTIONS: Each patient was hemodialyzed three times within 1 week with dialysates differing in calcium concentration only. Ultrafiltration was adjusted to achieve the same postdialysis weight. Immediately after dialysis, two-dimensionally targeted M-mode echocardiographic and calibrated carotid pulse tracings were recorded over a wide range of left ventricular end-systolic wall stress values (a measure of left ventricular afterload) generated by either methoxamine or nitroprusside. MEASUREMENTS AND MAIN RESULTS: After dialysis, three statistically distinct levels of Ca2+ were achieved. When Ca2+ was 1.34 +/- 0.03 mmol/L, Vcfc, calculated at a common level of afterload (sigma es = 50 g/cm2), was 1.01 +/- 0.05 cir/sec; at low Ca2+ (1.02 +/- 0.02 mmol/L), Vcfc fell to 0.89 +/- 0.04 cir/sec (P less than 0.001 compared with medium); at high Ca2+ (1.68 +/- 0.07 mmol/L) Vcfc rose to 1.10 +/- 0.03 circ/sec (P less than 0.001 compared with medium and low). CONCLUSION: Variations in Ca2+ are directly correlated with clinically significant changes in myocardial contractility.

Adult↗

Effect of intracoronary injections of sonicated microbubbles on left ventricular contractility.

Despite the recent interest in contrast-enhanced echocardiography as a means of defining myocardial perfusion, the effects of echo contrast agents on left ventricular (LV) contractility in humans remains poorly defined. This is particularly relevant because intracoronary injection of contrast agents used for angiographic visualization of coronary arteries produces significant alterations in LV hemodynamics. The relation of LV end-systolic wall stress (sigma es) to rate-corrected velocity of fiber shortening (Vcfc), a load-independent index of contractility, was studied in 7 patients undergoing elective coronary arteriography. Two-dimensional and targeted M-mode echocardiographic and central aortic pressure tracings were recorded during injections of standard volumes of angiographic (7 to 9 ml of nonsonicated Renografin-76) and echocardiographic (1.5 to 2.0 ml of sonicated Renografin-76) contrast agents into the left main coronary artery. The order in which agents were injected was randomly determined. Myocardial contractility was assessed under control conditions and 5 and 15 seconds after injection. Alterations in contractility relative to control were measured as the change in Vcfc after elimination of afterload (sigma es) as a confounding variable. An injection of Renografin-76 adequate for angiographic imaging of coronary artery anatomy resulted in a significant depression of LV contractility (p less than 0.001) in conjunction with a tendency toward increased afterload (p = 0.12); recovery occurred by 15 seconds after injection. The smaller amounts of sonicated Renografin-76 required to give adequate contrast enhancement of the myocardium did not alter LV contractile state or afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Echocardiographic contrast agents: effect of microbubbles and carrier solutions on left ventricular contractility.

Recently, there has been a resurgence of interest in the use of contrast-enhanced echocardiography as a means of noninvasively assessing myocardial perfusion. However, if injections of echocardiographic contrast agents are to be used for this purpose it is essential that they are not intrinsically toxic to the heart. In this study, the left ventricular end-systolic wall stress-rate-corrected velocity of fiber shortening relation, a load independent index of contractility, was studied in nine dogs. Two-dimensional and targeted M-mode echocardiographic as well as central aortic pressure tracings were made during echocardiographically gated, pressure- and volume-controlled aortic root injections of nonsonicated and sonicated Renografin-76, saline and dextrose 70% (n = 6), and sonicated and hand-agitated Renografin-76/saline mixture (n = 5). Two of nine dogs received all agents. Off-line computer videodensitometric analysis documented myocardial perfusion. In all cases, data were obtained at control and 5 and 15 seconds after injection. Additional data were collected at 25 seconds after injection for the Renografin-76/saline mixture. Alterations in contractility were measured relative to control as changes in rate-corrected velocity of fiber shortening after afterload (measured as end-systolic wall stress) was eliminated as a confounding variable. Under no condition did saline or Renografin-76 cause alterations in left ventricular contractility. Nonsonicated and sonicated dextrose 70% increased left ventricular contractility at 15 seconds but not at 5 seconds after injection. Hand-agitated Renografin-76/saline mixture induced a negative inotropic effect at 5 and 15 seconds after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Contrast ultrasonography of the kidney: a new method for evaluation of renal perfusion in vivo.

Assessment of the effects of pharmacologic agents on renal blood flow (RBF) is clinically important in many disease states, including hypertension and congestive heart failure. However, because of the complexities of RBF, quantitation in vivo has been technically difficult. This study demonstrates the utility of ultrasound imaging of the kidney combined with injection of a sonicated radiocontrast solution (Renografin-76) for the assessment of regional renal blood flow. The technique uses a suspension of uniform microbubbles (diameter 4.4 +/- 2.8 micron), which when injected directly into the descending aorta are distinctly visualized by renal ultrasound. Five dogs were studied. Catheters were placed in the descending aorta for injection of sonicated Renografin and in the renal artery for drug infusions. Data were collected before and during intrarenal artery infusions of bradykinin and norepinephrine. Total RBF was measured by electromagnetic flowmeter. Video density time curves were generated for comparable segments of the outer renal cortex and fit to a monoexponential decay curve. This allowed calculation of the mean exponential decay index (t1/2). An increase in t1/2 paralleled decreased renal perfusion (i.e., longer washout of contrast material). The opposite was true for a decrease in t1/2. Bradykinin increased RBF from 134 +/- 26 to 249 +/- 19 ml/min (p less than .01 vs control), and norepinephrine decreased RBF from 130 +/- 25 to 51 +/- 17 ml/min (p less than .01 vs control).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗