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Biomedical subjects

S Schuster

Publications and source records attributed to S Schuster.

At least 73 records · Page 4Linked to original sources

A pilot study of the biologic and therapeutic effects of granulocyte colony-stimulating factor (filgrastim) in patients with acute myelogenous leukemia.

In a carefully monitored pilot study, the in vivo biologic effects of filgrastim were investigated in eight patients with relapsed/refractory acute myelogenous leukemia. Within each patient, filgrastim was administered as a single agent prior to any chemotherapy in escalating doses of 0.12-6.0 micrograms/kg/day as a continuous intravenous infusion. The dose was increased every 14 days until an ANC of > or = 2500/mm3 had been achieved or there was evidence of proliferation of the leukemia. In patients who demonstrated growth of the leukemic clone, cytosine arabinoside was initiated at 200 mg/m2/day for 5 days. Through-out the course of therapy, the effects of filgrastim on maturation and proliferation were assessed by in vitro studies of bone marrow aspirates. Three patients demonstrated a sustained increase in ANC; one achieved a partial remission and remained on therapy for 31 weeks. Two of the three responding patients had hypocellular marrows at the time of initiating filgrastim and demonstrated a low but normal pattern of growth in CFU-GM assay early in the treatment course. This suggested that these two characteristics may define an environment in which filgrastim can induce a growth advantage for the normal residual hematopoietic elements. In this study of selected patients, filgrastim appeared safe.

Adult↗

Modular analysis of the control of complex metabolic pathways.

The understanding of the functioning of the intact cell would be simplified appreciably if it were possible first to analyze particular modules of cell physiology separately, and then to integrate the information so as to yield understanding of the control structure in terms of the mutual regulation of the modules. Here we develop a quantitative method based on Metabolic Control Analysis that makes this possible: The relevant properties of the modules are contained in "overall" elasticity coefficients, which reflect the changes in fluxes in the module upon a small variation of the environment of the module, allowing the latter to attain steady state. We show how overall control coefficients, which reflect the control exerted by the processes catalyzed by each module, can be expressed into the overall elasticity coefficients. We derive corresponding summation and connectivity theorems. A number of possible divisions of physiological systems into modules is discussed. This work is a generalization of previous analyses of overall control properties in that it allows for multiple fluxes to connect the modules, and reaction stoichiometries of any complexity.

Cell Physiological Phenomena↗

Endoventricular patch plasty improves results of LV aneurysmectomy.

From May 1985 to December 1991 52 patients were operated upon for postischemic left ventricular aneurysm (LV-A). Between May 1985 and July 1989 25 patients (group I) with a mean age of 59 (46-72) years underwent conventional aneurysmectomy with direct closure of the left ventricle (LV) and a mean of 1.9 (0-3) additional bypass grafts (54% triple-vessel disease). The hospital mortality was 8% (2/25) and the late mortality during a median follow-up time of 34 months was 28% (7/25) with a 4-year survival of 66%. Improvement in the quality of life (NYHA from 2.6 to 2.1, P = 0.078) and global left ventricular ejection fraction (EF) (from 35 to 38%) proved to be unsatisfactory in conjunction with the high late mortality rate. Between August 1989 and December 1991 a prospective series of 27 consecutive patients (group II) with a mean age of 61 (45-71) years underwent endoventricular patch plasty guided by two-dimensional transthoracic echocardiography (TTE) before and after surgery. The patch size and position were calculated preoperatively by measuring the distances from the mitral annulus to the infarct area which were reproduced during surgery with a simple ruler. A mean of 2.1 (0-4) bypass grafts were added with 62% of the patients having triple-vessel disease and 19% left main stenosis (P = 0.05, group I versus II). All patients have survived to date. One patient had to be excluded, giving a median follow-up time of 14 months for 26 patients. At the 6 months' control, the mean NYHA class was improved from 2.7 to 1.6, (P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Refined algorithm and computer program for calculating all non-negative fluxes admissible in steady states of biochemical reaction systems with or without some flux rates fixed.

A refined algorithm together with a computer procedure for determining the complete set of non-negative, steady-state fluxes in biochemical reaction systems of any complexity, with or without some flux rates fixed, is given. It is shown that this set is a convex polyhedron, which may or may not be bounde. The algorithm is illustrated by several examples; one of them concerns intermediary metabolism. A computer code in standard C is presented.

Algorithms↗

[Transesophageal echocardiography on the intensive care unit].

Transesophageal echocardiography is an important diagnostic tool available to the critical care physician. Indications for the use of transesophageal echocardiography in the intensive care unite include: critical illness and circulatory shock, thoracic aortic dissection, pulmonary embolism and endocarditis. Probe insertion is easy and is successful in 98% of intensive care patients. Further information concerning 44% of the patients was obtained with transesophageal as compared to transthoracic echocardiography. Transesophageal echocardiography is particularly helpful in evaluating cardiac size and function in patients with circulatory shock. When these patients are on multiple positive inotropic and vasopressor drugs, transesophageal echocardiography is useful in assessing left ventricular preload. In these patients, hemodynamic estimation of left ventricular filling may be misleading. More difficult is the assessment of hemodynamic events in patients requiring mechanical ventilation with increasing positive end-expiratory pressure (PEEP). This ventilation mode develops its own pathophysiology which superposes the effects of the underlying disease. Transesophageal examination of the heart after application of PEEP up to 16 cm H2O demonstrated an acute decrease in size of the right and left ventricle (Figure 1). Cardiac index was affected by the decrease in right ventricular dimension by external compression. The addition of positive and expiratory pressure to a level of 8 cm H2O did not depress cardiac index in patients with severe left ventricular dysfunction. PEEP ventilation is associated with abnormal filling patterns characterized by a significant reduction in peak early filling velocity, acceleration and deceleration rate of early filling and peak early to atrial filling velocity ratio (Figures 2a and 2b). Stoddard et al. showed, that these findings of transmitral Doppler flow indices are associated with abnormal left ventricular relaxation. Analysis of regional wall motion under different PEEP levels demonstrated a distinct transmission of increased intrathoracic pressure on the left ventricular wall. We found significant changes in systolic wall motion, in particular a decrease in systolic shortening of the septum and an increase of the lateral wall. Thus, increased intrathoracic pressure under PEEP ventilation is associated with nonuniform regional changes in systolic contraction and abnormal left ventricular relaxation. Both factors are responsible for the decrease in cardiac index under PEEP ventilation. Right ventricular infarction: The transgastric view is usefull in detecting right ventricular wall motion abnormalities and dilatation. Hemodynamically significant right ventricular infarction occurs in the posterior wall, which makes the transesophageal approach ideal. We studied a group of 39 patients with right ventricular infarction.(ABSTRACT TRUNCATED AT 400 WORDS)

Aortic Dissection↗

The definitions of metabolic control analysis revisited.

Various definitions of coefficients in metabolic control analysis are examined with respect to their theoretical consistency and practical applicability. We suggest agreement upon a definition for control coefficients which is clearly distinct from that for response coefficients, in such a way that the former describe inherent properties of the metabolic system while the latter refer to the influence of special parameters. Advantages and drawbacks of using normalized or non-normalized control coefficients are studied. It is shown that normalized control coefficients have the advantage of being invariant to a different rescaling of the particular fluxes. We demonstrate that some problems are easier to tackle if the consistency of time-independent control coefficients with their time-dependent counterparts is taken into account. It is shown that the matrix of flux control coefficients is an indempotent matrix. This allows an interpretation in terms of the transduction of the effect of parameter perturbations. Several aspects of the experimental measurement of control coefficients are discussed, with special reference to the different definitions.

Enzymes↗

[Computer-assisted analysis of wall motion of the right ventricle in a normal patient sample and diagnosis of right heart infarction using transesophageal echocardiography].

Using 2D and M-Mode transesophageal short axis cross sections, right ventricular systolic wall motion was quantified in 15 normal patients. A further group of 39 patients with right ventricular infarction was investigated. In the normal group fractional shortening of the septum was -19.6% (-45 to 8%), that of the lateral wall 51.6% (37 to 73%), of the posterior wall 33.9% (5 to 50%) and of the anterior wall 42.7% (18 to 57%). Right ventricular infarction (RVI) was associated in 33 patients with posterior left ventricular infarction (85%) and in three patients with anterior infarction. In two cases only an isolated RVI was found. Right ventricular dilation occurred in 24 patients (61%). Hemodynamic criteria were fulfilled in eleven out of 21 patients (53%). RVI was confirmed in one patient by surgery and in ten patients by autopsy. Recognition of regional wall motion abnormalities by transesophageal echocardiography permits an accurate bedside identification of RVI. 2D and M-Mode registration of the short axis improves RVI assessment. Wall motion analyses offer the possibility to determine the extent of right ventricular infarction.

Adult↗

Minimization of intermediate concentrations as a suggested optimality principle for biochemical networks. II. Time hierarchy, enzymatic rate laws, and erythrocyte metabolism.

The multiobjective problem of minimizing all intermediate concentrations is solved for a model of glycolysis, the pentose monophosphate shunt and the glutathione system in human erythrocytes. It turns out that one solution out of four obtained corresponds qualitatively to the real system. Furthermore, it is shown that for any reaction system, the mentioned optimality principle implies distinct time hierarchy in that some reactions are infinitely fast and subsist in quasi-equilibrium. Finally, the relationships to the standard method of deriving enzymatic rate laws are discussed.

Energy Metabolism↗

Lingual vibrotactile threshold shift differences between stutterers and normal speakers during magnitude-estimation scaling.

The purpose of this study was to investigate differences in tactile sensory system function between stutterers and normal speakers. This task was accomplished by studying possible tactile threshold shifts occurring during magnitude-estimation scaling of vibratory stimuli presented to the dorsal surface of the tongue. Ten normal speaking men (M age = 19.7 yr.) and 10 stutterers (M age = 25.9 yr.) participated. Analysis suggested that stutterers and normal speakers differ in terms of the responsiveness of the sensory mechanism for the lingual tactile threshold to vibratory stimulus intensities applied at suprathreshold levels. The stutterers and normal speakers performed similarly on all aspects of the magnitude-estimation scaling tasks, but the amount of threshold shift occurring during the scaling procedures was significantly greater for the stutterers at each suprathreshold intensity level employed.

Adolescent↗

[Thrombolysis in resuscitated patients with pulmonary embolism].

A retrospective analysis is presented of data from 17 patients with proven pulmonary embolism (10 women, 7 men, mean age 50.8 [18-76] years) who had received short-term high dosage thrombolytic therapy shortly before or after (less than 24 h) undergoing mechanical resuscitation. The mean duration of resuscitation was 76 (20-160) minutes. Two patients had already been resuscitated half an hour and one hour, respectively, before the commencement of thrombolysis. In nine other patients thrombolysis was commenced during resuscitation. Hospital mortality in the latter group was amazingly low (four of nine patients died). In contrast, out of six patients who required resuscitation shortly after the commencement of thrombolysis, not one survived. Haemorrhagic complications occurred in four out of the 17 patients, but only in two were they directly attributable to the resuscitation: one female patient developed an extensive haematoma in the sternal region, and two days after resuscitation another female patient had a haemorrhage into the capsule of the liver during thrombolytic therapy which had been continued because of leg vein thrombosis. In the light of these results it seems justifiable, even on mere clinical suspicion of pulmonary embolism, to initiate short-term high dosage thrombolytic therapy during or after resuscitation.

Adolescent↗