Rusconi, C., Faggiano, P., Sabatini, T. and Ghizzoni, G. (1991), High-Dose Nitrate Therapy in Patients with Severe Congestive- Heart-Failure - Acute Hemodynamic and Echo-Doppler Effects. Acp-Applied Cardiopulmonary Pathophysiology, 4 (1), 3-7.
Abstract: To test the hypothesis that nitroglycerin (NTG) may have a harmful effect on cardiac output (CO) in pts with CHF in whom previous treatment with diuretics and vasodilators considerably reduced left ventricular filling pressure (LVFP), we evaluated the hemodynamic effects of high-dose NTG infusion (283 +/- 147- mu-g/ml, range 100-500-mu-g/ml) in 8 pts with severe CHF (NYHA IV) already intensively treated towards a clinical stabilization. Echo-Doppler evaluation of transmitral flow was simultaneously performed measuring peak velocity during early filling (Evel) and atrial systole (Avel). Results: NTG infusion caused a significant reduction of right atrial pressure (4 +/- 3.5 versus - 1 +/- 4 mmHg, p < 0.001), pulmonary capillary wedge pressure (16 +/- 5 versus 7 +/- 3 mmHg, p < 0.001) and systemic vascular resistance (1500 +/- 329 versus 1320 +/- 330 dynes/s/cm-5). Stroke volume showed a not significant increase (62 +/- 18 versus 70 +/- 16 ml, ns); CO, blood pressure and heart rate did not show any significant change. Finally NTG infusion caused a significant decrease of Evel (0.66 +/- 0.2 versus 0.46 +/- 0.19, p < 0.001) and an increase of Avel (0.33 +/- 0.15 versus 0.41 +/- 0.16 m/s, p < 0.01); a significant correlation (r = 0.8) between Evel and PCWP was found. Conclusion: 1. In pts with severe CHF a marked reduction in LVFP by high dose NTG does not reduce CO. 2. Transmitral Echo-Doppler can give a noninvasive estimate of PCWP
Keywords: CARDIAC TRANSPLANTATION/CO/CONGESTIVE HEART FAILURE/DOPPLER ECHOCARDIOGRAPHY/MITRAL REGURGITATION/NETHERLANDS/NITRATES
Hevroy, O. and Klow, N.E. (1991), Left-Ventricular Diastolic Function During Short-Term Positive End-Expiratory Pressure Ventilation in Dogs. Acta Anaesthesiologica Scandinavica, 35 (4), 333-338.
Abstract: Simultaneous recordings of left ventricular (LV) pressure and volume (sonomicrometry) were made in acutely instrumented dogs anaesthetized with pentobarbital during intermittent positive pressure ventilation with zero and positive end-expiratory pressure at 10 and 20 cmH3O (PEEP10 and PEEP20). Pericardial pressure was measured continuously in order to obtain transmural LV pressure. PEEP reduced LV endiastolic volume and transmural pressure significantly. This was accompanied by significantly reduced stroke volume. LV peak diastolic filling rate, calculated as dV/dt(max), was significantly reduced when PEEP was applied, independent of LV volume alterations. LV diastolic compliance, assessed by the slope of LV pressure- volume relationship during LV filling, decreased significantly with increasing PEEP levels. A positive correlation was observed between reductions in peak diastolic filling rate and reductions in end-diastolic volume. The reduced peak diastolic filling rate, on the other hand, was closely correlated to reduced LV diastolic compliance. Isovolumetric relaxation rate (T) increased slightly at the highest PEEP level. This could, however, not be related to a reduced LV diastolic filling rate. The close association between reduced LV diastolic compliance and reduced diastolic filling rate may indicate that a tamponade-like effect is involved in the reduction of LV preload observed during PEEP ventilation
Keywords: CARDIAC-OUTPUT/COPENHAGEN/DENMARK/DISEASE/FALL/GEOMETRY/HEART-LUNG INTERACTION/ISOVOLUMETRIC RELAXATION RATE/ISOVOLUMIC RELAXATION/LEFT VENTRICULAR COMPLIANCE/LEFT VENTRICULAR DIASTOLIC FUNCTION/MECHANICAL VENTILATION/PEEP/PERICARDIAL PRESSURE/POSITIVE-EXPIRATORY PRESSURE/PRELOAD/TIME-COURSE/VOLUME RELATIONS
Dahlgren, G., Settergren, G., Ohqvist, G. and Brodin, L.A. (1991), A Comparative-Study of 5 Different Techniques to Reduce Left- Ventricular Dysfunction During Endotracheal Intubation. Acta Anaesthesiologica Scandinavica, 35 (7), 609-615.
Abstract: Thirty-five non-selected, consenting patients were studied during induction of anesthesia before coronary artery bypass grafting. Anesthesia was induced with diazepam, thiopentone and fentanyl, followed by pancuronium. Before induction, 200 MBq Tc-99 m - HSA was given i.v. and ejection fraction (EF) of the left ventricle was measured with a collimated single-crystal probe. The patients were allocated to five groups (seven patients in each) treated with: Group A: nitroglycerin i.v. bolus 4-mu-g x kg-1 given 30-60 s before laryngoscopy; Group B: nitroglycerin i.v. in continuous infusion, 1-mu-g x kg-1 x min- 1 started before induction; Group C: two-stage topical anesthesia of the vallecula region and larynx with lidocaine; Group D: a combination of nitroglycerin and topical anesthesia (as in Group B and C); and Group E: propranolol i.v. 0.01 mg x kg-1 given 5 min before intubation. All groups reacted in the same way during induction of anesthesia up to the point of laryngoscopy. End-diastolic volume and systemic arterial pressure decreased while cardiac index remained unchanged and EF increased. During laryngoscopy and intubation, however, differences between the groups were evident. Nitroglycerin i.v. as a bolus effectively prevented a reduction in EF and an increase in left ventricular volume. In addition to these beneficial hemodynamic effects, there was a moderate increase in heart rate and a reduction of stroke index. Continuous infusion of nitroglycerin and propranolol i.v. had no effect, since EF fell and left ventricular volume increased. Patients receiving topical anesthesia demonstrated a blunted response to endotracheal intubation with a moderate decrease in EF and an unchanged (Group C) or slightly increased (Group D) left ventricular volume
Keywords: BETA-ADRENERGIC BLOCKERS/BLOOD- PRESSURE RESPONSE/BYPASS-SURGERY/COPENHAGEN/CORONARY ARTERY DISEASE/CORONARY-ARTERY SURGERY/DENMARK/EJECTION FRACTION/ENDOTRACHEAL INTUBATION/FENTANYL-OXYGEN ANESTHESIA/INDUCTION/INTRAVENOUS ANESTHESIA/LARYNGOSCOPY/MYOCARDIAL ISCHEMIA/NITROGLYCERIN/RADIONUCLIDE ANGIOCARDIOGRAPHY/TOPICAL ANESTHESIA/TRACHEAL INTUBATION
Owall, A. and Sollevi, A. (1991), Myocardial Effects of Adenosine-Induced and Sodium Nitroprusside-Induced Hypotension - A Comparative-Study in Patients Anesthetized for Abdominal Aortic-Aneurysm Surgery. Acta Anaesthesiologica Scandinavica, 35 (3), 216-220.
Abstract: The effects of adenosine and sodium-nitroprusside (SNP) on central and myocardial haemodynamics and metabolism were evaluated during fentanyl anaesthesia (100-mu-g.kg-1) in six patients with peripheral vascular disease. The investigation was performed during stable anaeshtesia, before scheduled abdominal aortic graft surgery. Adenosine and SNP were infused intravenously in random order over 20 min, leaving a 30-min control period in between. The vasodilators were titrated in order to reduce mean arterial pressure by approximately 25%. Adenosine (90 +/- 20-mu-g.kg-1.min-1) reduced mean arterial pressure from 10.9 +/- 0.3 to 8.4 +/- 0.4 kPa (82 +/- 3 to 63 +/- 3 mmHg), and SNP (0.7 +/- 0.1-mu-g.kg-1.min-1) from 11.0 +/- 0.2 to 8.4 +/- 0.3 kPa (83 +/- 3 mmHg to 63 +/- 3 mmHg) during the hypotension period. Cardiac index remained unaffected during induced hypotension with both vasodilators, while heart rate increased during SNP infusion (8 +/- 3%) and remained unaffected with adenosine. Left ventricular stroke work index and myocardial oxygen consumption decreased during SNP infusion (33 +/- 3% and 17 +/- 5%, respectively), while these parameters were unchanged with adenosine. Adenosine hypotension increased coronary sinus flow 1-2 fold (128 +/- 26%), together with increased coronary sinus oxygen content (96 +/- 11%). In contrast, coronary sinus flow decreased during SNP hypotension (- 15 +/- 4%) with unaffected coronary sinus oxygen content. It is concluded that adenosine, in contrast to SNP, is associated with a hyperkinetic myocardial circulation
Keywords: ADENOSINE/ANESTHESIA/BLOOD-FLOW/CONTROLLED/COPENHAGEN/CORONARY CIRCULATION/CORONARY-ARTERY DISEASE/DENMARK/DISCONTINUATION/HEMODYNAMICS/HYPERTENSION/HYPOTENSION/ISOFLURANE/NITROGLYCERIN/NITROPRUSSIDE/STEAL/TRIPHOSPHATE
Vanderlinden, P., Gilbart, E., Engelman, E., Derood, M. and Vincent, J.L. (1991), Adrenergic Support During Anesthesia in Experimental Endotoxin- Shock - Norepinephrine Versus Dobutamine. Acta Anaesthesiologica Scandinavica, 35 (2), 134-140.
Abstract: The effects of norepinephrine and dobutamine were compared during endotoxin shock in dogs anesthetized either with enflurane (E: 1.5%, N = 12) or with i.v. ketamine (K: 5 mg . kg-1 + 0.2 mg . kg-1 . min-1, N = 12). An i.v. bolus of 1.5 mg.kg-1 E. coli endotoxin was followed by saline infusion to restore left-sided filling pressures at baseline. With E, heart rate, mean arterial pressure and stroke index decreased (P < 0.01). The decrease in oxygen delivery (Do2) and in oxygen consumption (Vo2) was associated with an increase in blood lactate. In contrast, K anethesia was associated with remarkable hemodynamic stability. Do2 was well maintained, Vo2 decreased (P < 0.01) and blood lactate did not change. Under E anethesia, mean arterial pressure increased more with norepinephrine and heart rate increased more with dobutamine. Under K anesthesia, cardiac index, stroke index and left ventricular stroke work index increased similarly with both agents. In both groups Do2 and Vo2 increased markedly. The amount of fluid infused was higher with dobutamine than with norepinephrine. Thus, enflurane but not ketamine had depressant cardiovascular effects at the doses used in this model. With both anesthetics, norpinephrine and dobutamine could effectively improve cardiac function. Dobutamine could therefore represent a valuable alternative to norepinephrine for cardiovascular support during anesthesia in septic shock
Keywords: ADRENERGIC AGENTS/ANESTHESIA/BLOOD-FLOW/COPENHAGEN/DELIVERY/DENMARK/DOBUTAMINE/DOPAMINE/ENFLURANE/EXPERIMENTAL SEPTIC SHOCK/HALOTHANE/INHALATION/INTRAVENOUS/ISOFLURANE/KETAMINE/METABOLISM/NOREPINEPHRINE/OXYGEN-CONSUMPTION/SEPTIC/SHOCK/SYMPATHOMIMETICS
Mano, T., Iwase, S., Saito, M., Koga, K., Abe, H., Inamura, K. and Matsukawa, T. (1991), Neural and Humoral Controlling Mechanisms of Cardiovascular Functions in Man Under Weightlessness Simulated by Water Immersion. Acta Astronautica, 23 31-33.
Abstract: To clarify how neural and humoral mechanisms operate to control cardiovascular unctions in man under weightlessness, the response of sympathetic nerve activity was observed in healthy human subjects by means of microneurographic technique with the changes of several hemodynamic parameters and hormonal responses during thermoneutral head-out water immersion. Muscle sympathetic nerve activity was markedly suppressed by head-out immersion, concomitantly with a reduction of the leg volume, an increase of the stroke volume and a reduction of total peripheral resistance. At the same time, plasma level of norepinephrine, vasopressive and antidiuretic hormones (ADH, aldosterone, renin activity, angiotensin I.II) were reduced, while vasodepressive and diuretic hormone (ANP) was markedly increased. The systemic blood pressure was maintained almost unchanged during head-out water immersion. The suppressive response of sympathetic nerve activity seemed to be age- dependent. This response was less prominent in the elderly than in young subjects. It is concluded that the suppressive response of muscle sympathetic activity plays an important role to maintain hemodynamic homeostasis under weightlessness to compensate for the cephalad fluid shift and the resultant increase of the stroke volume in cooperation with the hormonal responses
Arbeille, P., Lebouard, D., Massabuau, M., Pottier, J.M., Patat, F., Pourcelot, L. and Guell, A. (1991), Effect on the Cardiac-Function of Repeated Lbnp During A 1- Month Head Down Tilt. Acta Astronautica , 25 (7), 415-418.
Abstract: Cardiovascular assessment by ultrasound methods was performed during two long duration (1 month) Head Down Tilt (HDT) on 6 healthy volunteers. On a first 1 month HDT session, 3 of the 6 subjects (A, B, C) had daily several lower body negative pressure tests (LBNP), whereas the 3 subjects remaining (D, E, F) rested without LBNP. On a second 1 month HDT session subjects D, E, and F had daily LBNP tests and the A, B and C subjects did not. The cardiac function was assessed by Echocardiography (B mode, TM mode). On all the "6 non LBNP" subjects the left ventricule diastolic volume (LVDV), the stroke volume (SV) and the cardiac output (CO) increase (+ 10%, -15%) after HDT then decrease and remain inferior (-5%, -5%) or equal to the basal value during the HDT. Immediately after the end of the HDT the heart rate (HR) increase (+ 10%, +30%) whereas the cardiac parameters decrease weakly (-5%, -10%) and normalize after 3 days of recovery. On the "6 LBNP" subjects the LVDV, SV and CO increase (+ 10%, + 15%) after 1 h HDT as in the previous group then decrease but remain superior (+ 5%, + 15%) or equal to the basal value. After the HDT session, the HR is markedly increased (+ 20%, + 40%) the LVDV and SV decrease (-15%, -20%) whereas the CO increases or decreases depending on the amplitude of the HR variations. These parameters do not completely normalize after 3 days recovery. Repeated LBNP sessions have a significant effect on the cardiovascular function as it maintains all cardiac parameters above the basal value. The LBNP manoeuvre can be considered as an efficient countermeasure to prevent cardiac disadaptation induced by HDT position and probably microgravity
Kooloos, J.G.M. and Zweers, G.A. (1991), Integration of Pecking, Filter Feeding and Drinking Mechanisms in Waterfowl. Acta Biotheoretica, 39 (2), 107-140.
Abstract: This paper is one of several contributions in a series, illustrating the application of a specific deductive methodology to explain diversity of form. The methodology facilitates the explanation of feeding morphologies in various ducks as a transformation of the mallard's feeding design maximized for specific proportions of performance that are contributed by pecking and filter feeding mechanisms. The earlier described anatomy and formal analyses of the three mechanisms in the mallard served as the initial conditions used in simulation models. Four elements of the feeding system were chosen that play a major role in all three mechanisms. For each element, the main parameter was selected: storage capacity of the rostral mouth cavity, transport capacity of the rostral mouth tube, storage capacity of the caudal mouth cavity and transport capacity of the caudal mouth tube. The, boundary conditions for the simulation were determined from internal organismic constraints. The total food uptake of the mallard was regarded as the function to be maximized. This 'object' function is the summation of the food uptake by one second of pecking and one second of filter feeding. The drinking mechanism was shown not to interfere, since that mechanism operates sufficiently whenever the pumping mechanism works properly. The 'object' function, made up by the pecking and filter feeding performances was graphed. From these graphs a morphospace was developed: the region within which modifications of the mouth design are feasible. This procedure allowed examination of the general hypothesis that different modifications of one design for a complex multi-role system are explainable from differences in proportions of the functional performance contributed by each of the roles. Two predictions were evaluated more specifically: 1) If filter feeding performance must increase for a specific change in total food uptake, the volume of the rostral mouth cavity must increase; this requires widening and lengthening of the rostral maxillar portion and also a phase shift in jaw and lingual motion patterns, increasing the stroke volume. 2) If pecking performance must increase, the transport capacity of the rostral mouth tube must increase; this requires shortening of the maxillar mid portion. These two predictions regarding change in mouth morphology were borne Out by shovelers and tufted ducks, respectively. The deductive analysis of the feeding system's morphospace allowed the explanation of the wide diversity of forms in the duck mouth designs as emerging from the great radiation capacity of the ancestral duck's mouth design: it is a versatile, potentially multi-role system in which pecking, drinking and filter feeding mechanisms are mutually very tolerant and, by epiphenomena, includes the elements of a grazing mechanism. In addition, the deduced morphospace was shown to explain phenotypic plasticity, since it explains the occurrence of two morphotypes that develop due to habitat discrimination: one type that has been forced to filter feed, and one type that feeds by pecking
Keywords: AYTHYA- FULIGULA/EXPLANATION/MALLARD ANAS-PLATYRHYNCHOS/MORPHOLOGY/NETHERLANDS/PIGEON COLUMBA-LIVIA
Primo, G., Leclerc, J.L., Antoine, M., Desmet, J.M. and Joris, M. (1991), A Survey of 9 Years Heart-Transplantation at Erasme Hospital, University-Of-Brussels. Acta Cardiologica, 46 (5), 555-565.
Abstract: Between March 1982 and March 1991, 225 heart transplantations (HTx) have been performed in 220 patients suffering end stage cardiac disease. Thirteen percent were females and 87% were males. Age range was from 5 to 68 years. The underlying cardiac disease was ischemic cardiopathy in 51.5%, congestive dilated cardiomyopathy in 42%, valvular cardiomyopathy in 3.5%, toxic myocarditis (post-adriamycin) in 1.5% and chronic rejection in 2.5% (retransplantation). Selection of the recipients was done following the currently well established criteria also taking into account the absolute major contraindications for HTx. Due to the still increasing demand of donor organs, currently donor age has been extended up to 50 years for male and 55 years for female donors. One quarter of the grafts were harvested on site in our institution, two other quarters were harvested somewhere else in Belgium and the last quarter provided by other countries cooperating with Eurotransplant. All patients have undergone orthotopic cardiac transplantation using the standard Lower and Shumway technique. Immunosuppression protocols have changed four times throughout the years. Nevertheless all were based on the use of Ciclosporine variously combined with other current immunosuppressive drugs. Rejection monitoring relied on routine endocardiac biopsy and was diagnosed according to the Billingham criteria. The in-hospital mortality is currently 11%. Infection, early right heart graft failure and accute rejection were the leading causes of death. The major causes of early morbidity were several curable infections, reversible rejection episodes, transient acute renal failure and controlable arterial hypertension. Among the survivors followed for at least one month up to nine years, half of late mortality was caused by chronic rejection followed by infection, sudden death, metabolic disorders, stroke and malignancy. Late morbidity involves cases of mild coronary graft diseases, biological renal insufficiency, some degree of arterial hypertension, dislipidemia. Current actuarial survival rate is 87% at one year, 76% at 5 years up to 9 years. Our experience confirms that HTx represents today and effective therapy for selected patients suffering end stage cardiac disease
Keywords: BELGIUM/CARDIAC/HEART TRANSPLANTATION/IMMUNOSUPPRESSION/RESULTS/SURVIVAL
Goldstein, M., Vincent, J.L., Goldstein, J., Leclerc, J.L., Primo, G. and Kahn, R.J. (1991), Echocardiographic Signs of Cardiac Rejection During the 1St Week After Cardiac Transplantation. Acta Cardiologica, 46 (2), 179-188.
Abstract: The early recognition of acute rejection after heart transplantation remains an important clinical problem. In this study we explored the value of echo-Doppler techniques to identify the rejection during the first week after cardiac transplantation. The study included 22 patients with an average age of 48 +/- 9 years. Ultrasonic measurements were obtained by 2-dimensional 84-degrees phased array sector scanner with pulsed Doppler incorporated. The stroke index (SI), the peak outflow blood velocity pulsed (POBVP), the peak outflow blood acceleration pulsed (POBAP), the peak flow velocity in early diastole (PFVE), the peak flow velocity during atrial systole (PFVA), the PFVA\PFVE ratio, the mitral valve pressure half-time (PHT) and the fractional shortening (FS) were calculated. On the seventh day after transplantation, a percutaneous right ventricular endomyocardial biopsy was systematically performed. For the entire group, the SI, PHT and the FS relation were not significantly influenced during the week of evaluation. The POBVP and the POBAP transiently decreased but returned to baseline on the seventh day. An increment in the PFVA/PFVE ratio was observed in 4 patients, and acute allograft rejection was documented in 3 of them. On day 7 after transplantation, PFVA and PFVA/PFVE were significantly higher in patients with rejection. No patient with normal PFVA/PFVE ratio had allograft rejection. No patient with rejection showed signs of altered systolic function as measured by SI, POBVP, POBAP and FS. These data therefore indicate that the assessment of the diastolic function using Doppler techniques (PFVA/PFVE) can be helpful to detect signs of acute allograft rejection occurring early after heart transplant
Keywords: BELGIUM/CARDIAC REJECTION/CARDIAC TRANSPLANTATION/ECHOCARDIOGRAPHIC SIGNS
Ceda, G.P., Ceresini, G., Denti, L., Magnani, D., Marchini, L., Valenti, G. and Hoffman, A.R. (1991), Effects of Cytidine 5'-Diphosphocholine Administration on Basal and Growth Hormone-Releasing Hormone-Induced Growth-Hormone Secretion in Elderly Subjects. Acta Endocrinologica, 124 (5), 516-520.
Abstract: The basal and GH-releasing hormone-stimulated secretion of GH declines in the elderly. We tested the ability of cytidine 5'- diphosphocholine, a drug used in the treatment of stroke and Parkinson's disease, to alter GH secretion in 11 healthy elderly volunteers, aged 69-84. Each subject received an iv infusion of 2 g of cytidine 5'-diphosphocholine or normal saline. GHRH and TRH were also administered during cytidine 5'-diphosphocholine infusions. The infusion of cytidine 5'- diphosphocholine induced a 4-fold (p < 0.05) increase in serum GH levels over basal values. A small increase in GH was seen after GHRH administration. However, the addition of GHRH to the cytidine 5'-diphosphocholine infusion resulted in a GH response which was significantly greater than that seen after GHRH alone; the integrated concentration of GH was more than 2- fold greater in the cytidine 5'-diphosphocholine treated group (706.85 +/- 185.1 vs 248.9 +/- 61.4-mu-g.l-1. (120 min)-1; p = 0.01). The PRL and TSH responses to TRH were not significantly affected by cytidine 5'-diphosphocholine infusion, indicating that dopaminergic mechanisms are not involved. These studies demonstrate that cytidine 5'-diphosphocholine can enhance basal and GHRH-stimulated GH release in the elderly, but the mechanism of action of the drug remains unclear
Finelli, C., Palareti, G., Poggi, M., Torricelli, P., Vianelli, N., Fiacchini, M., Zuffa, E., Ricci, P., Gugliotta, L., Coccheri, S. and Tura, S. (1991), Ticlopidine Lowers Plasma-Fibrinogen in Patients with Polycythemia-Rubra-Vera and Additional Thrombotic Risk-Factors - A Double-Blind Controlled-Study. Acta Haematologica, 85 (3), 113-118.
Abstract: Thirty-seven patients affected by polycythaemia rubra vera (PRV) and with at least one additional thrombotic risk factor (overt vascular disease, diabetes mellitus, treated hypertension, smoking habit, plasma hyperviscosity, hyperfibrinogenemia) were enrolled in a double-blind randomized placebo-controlled study, and 18 were given ticlopidine 250 mg, b.i.d., for 60 days. All the patients had previously been submitted to cytoreduction, and PRV was under control in all cases at the start of the study. During the study, the haematological parameters were controlled every 15 days, and venesection was performed if haematocrit was > 46%. Whole blood viscosity, at low and high shear rates, plasma viscosity, and fibrinogen were measured on days 0 and 60. In the ticlopidine group, we recorded a significant 13.14% reduction of the mean fibrinogen level after treatment (390 +/- 63 vs. 449 +/- 97 mg/dl, p < 0.01). All the other haemorheological parameters were not significantly modified by ticlopidine treatment, nor were there significant modifications recorded in the placebo group. Our study shows that ticlopidine may reduce a probable thrombotic risk factor (hyperfibrinogenemia) in PRV patients
Keywords: ASPIRIN/COMPLICATIONS/DISEASE/INTERMITTENT CLAUDICATION/MYELOPROLIFERATIVE DISORDERS/PLASMA FIBRINOGEN/PLASMA VISCOSITY/PLATELET-FUNCTION/POLYCYTHEMIA-RUBRA-VERA/POLYCYTHEMIA-VERA/PREVENTION/STROKE/SWITZERLAND/TICLOPIDINE/WHOLE BLOOD VISCOSITY
Minar, E. (1991), Prevention of Cerebrovascular-Disease. Acta Medica Austriaca, 18 (2), 38-&.
Abstract: The decision for the optimal preventive and therapeutic interventions in cerebrovascular disease depends on the underlying disease process. Therefore it is important to identify the different pathomechanisms by modern techniques. The significantly increased cardiovascular risk of patients with atherosclerotic extracranial arterial disease - even when neurologically asymptomatic - makes identification and elimination of all vascular risk factors of crucial importance for primary and secondary prevention. The low risk of stroke without prior transient ischemic attacks makes prophylactic carotid surgery not advisable in asymptomatic patients. Regular controls by sonography are necessary to identify patients with progression of carotid stenosis, and the patients should be informed about warning symptoms of threatening stroke. Secondary prevention with antiplatelet agents (aspirin, ticlopidine) proved effective in patients with cerebrovascular diseases by significant reduction in mortality and in the incidence of stroke and myocardial infarction. The optimum dose of aspirin is not known. Patients with atherosclerotic lesions of the major cerebral arteries have not been shown convincingly to benefit from long-term anticoagulation, while the risk of bleeding complications is increased significantly. Major clinical trials have been initiated to evaluate the benefit of carotid endarterectomy. Anticoagulation therapy can reduce the risk of cardiogenic emboli. Recently it was demonstrated that also aspirin seems effective in reducing incidence of thromboembolic complications in patients with chronic atrial fibrillation. The start of anticoagulant therapy after cerebral embolism depends mainly on CT scan findings
Keywords: ANTICOAGULANT- THERAPY/ANTICOAGULATION/ANTIPLATELET AGENTS/ANTITHROMBOTIC THERAPY/CARDIOGENIC EMBOLISM/CAROTID-ARTERY/CEREBRAL-ISCHEMIA/CEREBROVASCULAR DISEASE/CHRONIC ATRIAL-FIBRILLATION/CT/LOW- DOSE ASPIRIN/NATURAL-HISTORY/PREVENTION/RANDOMIZED TRIAL/SECONDARY PREVENTION/TRANSIENT ISCHEMIC ATTACKS
Hennerici, M., Mess, W. and Rautenberg, W. (1991), Cerebrovascular Diseases - Signs, Syndromes and Follow-Up. Acta Medica Austriaca, 18 (2), 34-&.
Abstract: The observation of the spontaneous course of the extracranial vascular process as a characteristic cause of cerebral ischemia has shown that vascular changes occur largely independently from the appearance of cerebral functional disturbances in the associated vascular territory. Hemodynamic factors play a minor role; while with the present standard methods available, embolic mechanisms can be insufficiently analyzed. The prospective developmental observations of morphologic and fluid-dynamic aspects and supplemental cell biology and metabolic analysis provide new criteria for an individual risk evaluation of the various mechanisms causing pathologically different cerebral function disturbances, and their analysis has crucial significance for a therapy plan
Keywords: ARTERIAL-DISEASE/BRUITS/CAROTID ENDARTERECTOMY/CEREBRAL EMBOLISM/CEREBRAL ISCHEMIA/NATURAL-HISTORY/STROKE
Wimberger, D., Kramer, J., Prayer, L., Stiglbauer, R. and Imhof, H. (1991), Mri Diagnosis of Cerebrovascular Diseases. Acta Medica Austriaca, 18 (2), 29-34.
Abstract: Regarding cerebrovascular diseases magnetic resonance imaging (MRI) provides informations which could not be obtained before by any other imaging method. MRI permits an early detection of ischemic infarctions, exact delineation of lesions near to skull base, and microangiopathy. Further diagnosis of arteriovenous malformations and venous thromboses can be done without using contrast media. Exclusion of acute hemorrhage or subarachnoidal hemor- rhage is still a domain of computed tomography (CT). Other MR methods, like magnetic resonance angiography (MRA) and magnetic resonance spectroscopy (MRS) are expected to replace angiography and positron emission tomography (PET) in the near future, at least for some purposes
Keywords: ANGIOGRAPHY/BRAIN/CEREBRAL INFARCTION/CEREBROVASCULAR DISEASES/CT/LACUNAR INFARCTION/MAGNETIC RESONANCE ANGIOGRAPHY/MAGNETIC RESONANCE TOMOGRAPHY/MAGNETIC-RESONANCE/MICROANGIOGRAPHY/MR/MRI/PET/SPACES/STROKE
Polterauer, P., Prager, M., Kretschmer, G. and Huk, I. (1991), Stroke Prevention by Carotid-Artery Endarterectomy - Technique, Indication, Results. Acta Medica Austriaca, 18 (2), 51-55.
Abstract: Carotid artery endarterectomy (CAE) is a surgical standard procedure today. The indication is the symptomatic patient (Stage II) with transient ischemic attacks (TIA) and stenosis of the internal carotid artery (ACI). Data of several studies have yielded a highly restrictive policy toward operative procedures in asymptomatic patients (Stage I) with carotid bruit or ACI-stenosis. Furthermore there emerged wide consensus, that patients with frank stroke (Stage III) should not be operated upon. As diagnostic procedures highly advanced non invasive procedures came up during the last decade, as well as computerized tomography and digital substraction angiography. The operative procedure is performed in general anesthesia with controlled hypertension during the clamping period (n = 650). Perioperative results without using a shunt are not different to those with a shunt. During the last 5 year period our results yielded a 1% perioperative central permanent neurological deficit rate (CPNDR) and a 1% operative mortality. During a 51 months median observation period 1.5% presented again with transient ischemic attacks-with TIA; 0.6% developed a stroke and 2.2% decreased by cerebral complications yielding at totally 4.3% long term complication rate. The annual rates are 0.3%, 0.1% respectively 0.5%, totally 0.9%. In conclusion CAE can be offered as a safe surgical stroke preventing procedure in symptomatic TIA patients with ACI stenoses in our institution. Perioperative as well as long term results are yielding a high standard and are clearly better than those without operation
Keywords: CAROTID ARTERY ENDARTERECTOMY/CEREBROVASCULAR INSUFFICIENCY/DISEASE/RISK/SHUNT/TIA/TRANSIENT ISCHEMIC ATTACKS
Lechleitner, M. and Braunsteiner, H. (1991), Cerebrovascular Disorders As A Manifestation of A Common Disease. Acta Medica Austriaca, 18 (2), 47-&.
Abstract: During the last years several risk factors for cerebrovascular disease (CVI) could be identified by epidemiologic studies; the incidence of CVI, like that of coronary artery disease, seems to be closely related to high blood pressure, hyperlipidaemia, smoking and diabetes mellitus. The diagnostic difficulties in CVI, especially concerning the localization and size of vascular lesions, explain controversal results in the evaluation of different clinical studies. A comparison of these results is often hard to perform also out of the different statistical methods applied in the various trials. The development of improved diagnostic methods, especially ultrasonography, which allow a better definition of disease processes, offers an advantage for controlled screening and intervention trials. After all further improvements in disease prevention as well as in diagnostic and therapeutic procedures require an intensive co-operation between internal medicine and neurology
Keywords: ADULTS/CAROTID-ARTERY ATHEROSCLEROSIS/CEREBROVASCULAR DISORDERS/CORONARY HEART-DISEASE/FACTOR INTERVENTION TRIAL/FOLLOW- UP/MEN/MORTALITY/PREDISPOSITION/RISK FACTOR/RISK FACTORS/SERUM-CHOLESTEROL/STROKE
Horvath, M., Boszormenyi, E., Karman, M., Berenyi, I., Molnar, J., Pszota, A., Szalai, M. and Nemeth, L. (1991), Tc-99M (Dupont Cardiolite) Investigations in Postinfarction Patients with Holter-Checked Silent Ischemia. Acta Medica Hungarica, 48 (1-2), 61-72.
Abstract: Sixteen middle-aged, normotensive, slightly overweight male patients with previous myocaridal infarction were studied during Holter-checked silent myocardial ischaemia. As reference, stress and late 201-T1 scintigraphy served for comparison with Cardiolite-MIBI silent ischaemic perfusion scan, both carried out in planar mode. The circumferential profiles differed in 9 cases, on region of interest basis the segment number difference was 10, but the late distribution segment number was near to both ischaemic numbers. The quantitative scores were distinctive (ratio 133-128/103) indicating the silent ischaemia appeared in the peri-infarct area. The silent ischaemic MIBI and stress 201-T1 ischaemic score difference was reduced by means of repeated SPECT investigation. With gated radionuclide ventriculography there was -4.3% difference between the left ventricular ejection fractions, measured with first pass MIBI technique during silent ischaemia and afterwards in basal state. The impairment of the left ventricular function was reflected on the stroke pattern of our Holter-based radiocyclogram, as well. Taking the 43.7-48.0 = -4.3% "ischaemic shift" into consideration it was a close correlation (r = 0.90) between the two kinds of ejection fraction determination. The major rhythm failures (occurring during the 24 h Holter monitoring) decreased to a higher degree the left ventricular ejection fraction than silent ischaemia or silent ischaemia and minor rhythm failure together (38-42-50%)
Keywords: HOLTER-CONTROLLED SILENT ISCHEMIC PERIODS ON POSTINFARCTION PATIENTS/LEFT VENTRICULAR EJECTION FRACTION/MYOCARDIAL PERFUSION/RADIOCYCLOGRAPHIC CONTRACTION DYNAMIC ANALYSIS/SPECT/STATE/TC-99M METHOXY-ISOBUTYL-ISONITRILE INVESTIGATIONS
Gondos, T., Szabo, K., Jokkel, G. and Penzes, I. (1991), Outcome Prediction in Adult Respiratory-Distress Syndrome Using Discriminant-Analysis of Cardiorespiratory Data. Acta Medica Hungarica, 48 (1-2), 51-60.
Abstract: In order to examine the prognostic value of different cardiopulmonary variables in adult respiratory distress syndrome the data of 30 patients with this illness were studied retrospectively. The patients were divided into 3 groups: Group A: survivors (9 cases, 40 examinations), Group B: early stage nonsurvivors (8 cases, 37 examinations), Group C: late stage nonsurvivors (19 cases, 89 examinations). In 6 nonsurvivor patients a few measurements were done in the early and late stage, too. There were highly significant differences between Groups A and C (mean pulmonary arterial pressure, pulmonary arterial diastolic pressure minus pulmonary capillary wedge pressure, left ventricular stroke work index, systemic and pulmonary vascular resistance, inspired oxygen fraction, arterial oxygen tension per inspired oxygen fraction, mixed venous oxygen saturation, pulmonary shunt fraction, and oxygen delivery, but the differences in relation to other groups were less prominent. Using a step-wise discriminant analysis, it was found that the oxygenation parameters alone determined the outcome correctly in 68-75%. Extending the analysis to haemodynamic variables the result improved (72-80%). Similar prediction was obtained when parameters potentionally measurable by noninvasive methods were analysed (69-80%). These results suggest that it is possible to predict the outcome of ARDS correctly without any invasive monitoring technique
Keywords: ARDS/DISCRIMINANT ANALYSIS/HEMODYNAMICS/OXYGENATION/PROGNOSIS PREDICTION
Shigenobu, M., Nakayama, H., Hisamochi, K., Yamamoto, N., Senoo, Y. and Teramoto, S. (1991), Doppler Echocardiographic Evaluation of Bjork-Shiley and St Jude Medical Prostheses in the Mitral Position. Acta Medica Okayama, 45 (5), 325-332.
Abstract: The left ventricular studies by Doppler echocardiography were performed in 50 patients with a Bjork-Shiley (B-S) mitral valve and 50 patients after implantation of a St. Jude Medical (SJM) mitral valve; the effect of valve replacement on the hemodynamic performance at rest and during bicycle exercise was determined from serial echocardiographic data. Twenty-eight patients (56%) of the B-S group and 42 patients (84%) of the SJM group showed a good response to the exercise. There was no significant difference in the effective orifice area at rest among each sizes of the B-S valve. In the SJM valve, on the contrary, the effective valve orifice area increases in parallel to the size of the SJM valve. There was a clear relation between the valve size and pressure gradient. The pressure gradient directly depends on the valve size and the effective orifice area in the SJM valve. High pressure gradient group in both prostheses had a tendency to take negative values of percent increase in stroke volume. Further, there were no cases showing positive values of percent increase in enddiastolic volume among the patients whose pressure gradients were assumed to be more than 10 mmHg at rest. It is suggested that impairment of inflow caused by the artificial valve, prosthetic valve stenosis, is possibly a significant factor causing left ventricular dysfunction, notably a decrease in stroke volume during exercise. In the B-S group, 8 out of 50 patients underwent reoperation because of unacceptably high pressure gradients across the mitral valve prosthesis caused by the thrombus and tissue ingrowth, while reoperation was not required in the SJM group. We conclude that the high pressure gradient group is considered to be a reserved cohort of reoperative surgery and Doppler echocardiography can detect those patients before they become significantly impaired
Keywords: BJORK-SHILEY VALVE/BS/DOPPLER ECHOCARDIOGRAPHY/JAPAN/PHARMACOLOGY/PROSTHETIC MITRAL VALVE STENOSIS/ST JUDE MEDICAL VALVE/ULTRASOUND/VALVE
Ishino, K., Murakami, T., Nakayama, H., Yamada, M., Morimoto, T., Hisamochi, K., Tanaka, T., Senoo, Y. and Teramoto, S. (1991), A Sheep Survived for 48 Days with the Biventricular Bypass Type Total Artificial-Heart. Acta Medica Okayama, 45 (4), 223-231.
Abstract: A biventricular bypass type total artificial heart (BVB-TAH) utilizing two pusher-plate pumps was developed and implanted in a sheep for 48 days with excellent results. A Hall effect sensor was utilized to operate each pump independently with a full stroke at variable rates (VR). With this system, the animal's hemodynamics was kept physiologically, and all metabolic parameters except hemoglobin and hematocrit returned to normal three weeks after implantation. However, signs of infection appeared on the forty-second day, and consequently the animal fell into a state of shock. Even at that time the BVB-TAH maintained circulation by increasing pumping rate automatically. On the forty-eighth day, the animal could not stand and suffered from anuria; the experiment was then terminated after 1,140 h pumping. At autopsy, there was an enlarged heart with an atrophic change, 1,900 ml of pleural effusion, and 3,100 ml of ascites fluid. Blood culture taken on the forty-seventh day yielded Acinetobacter calcoaceticus. The BVB-TAH operated in an independent VR mode maintained entire circulation, and has a capability of substituting the native heart function in any situation
Keywords: BIVENTRICULAR BYPASS/CLINICAL USE/HALL EFFECT SENSOR/JAPAN/PHARMACOLOGY/PUSHER-PLATE PUMP/TOTAL ARTIFICIAL HEART/VARIABLE RATE MODE
Kawamura, S., Yasui, N., Shirasawa, M. and Fukasawa, H. (1991), Rat Middle Cerebral-Artery Occlusion Using An Intraluminal Thread Technique. Acta Neurochirurgica, 109 (3-4), 126-132.
Abstract: A modification of the previous methods of producing cerebral ischaemia in rats (Koizumi et al., Longa et al.), using an intraluminal thread technique, is described. The middle cerebral artery is occluded by introducing a simple 3-0 nylon thread (0.20-0.249 mm in diameter) through the internal carotid artery in the neck. It has been proven that with this method reproducible focal cerebral ischaemia can be achieved which resembles human stroke. Therefore this simple and relatively non-invasive model is suitable for the pathophysiological investigation of ischaemic stroke and the testing of potential therapies
Keywords: BLOOD/BRAIN/BRAIN ISCHEMIA/CEREBRAL EDEMA/CEREBRAL ISCHEMIA/MIDDLE CEREBRAL ARTERY OCCLUSION/RATS
Deruty, R., Mottolese, C., Pelissouguyotat, I. and Lapras, C. (1991), The Carotid Endarterectomy - Experience with 260 Cases and Discussion of the Indications. Acta Neurochirurgica, 112 (1-2), 1-7.
Abstract: During 1978 to 1989, 235 patients were operated upon with 260 procedures for cervical carotid endarterectomy. The patients were classified according to the presence or absence of ischaemic symptomatology, and for symptomatic patients, according to the reversibility or persistance of ischaemic symptoms. So the selection of patients was: reversible ischaemia 46%, stroke 29%, asymptomatic patients 25%. In the stroke group, no patient was operated on as an emergency, the endarterectomy was only performed after stabilization of the clinical state. Three subgroups were included in patients operated on for asymptomatic carotid stenosis: casual discovery 40%, treatment of the second carotid artery (previous endarterectomy for symptomatic contralateral stenosis) 34%, and treatment of the second carotid artery (previous ECIC by-pass for contralateral carotid occlusion) 26%. All patients were operated upon after angiographic exploration (femoral catheterisation in most cases), and after cerebral CT scan. The surgical technique included general anaesthesia, systematic shunting, endarterectomy after longitudinal arteriotomy, closure without patch. The operating microscope has been used since 1985. The surgical results were studied in terms of uneventful postoperative course (87%), reversible complications (8%) and long lasting complications (5%). The long lasting complications were of local origin (1%), of neurological origin (2%), of general origin (1%). Overall the operative outcome at 6 months was: return to previous clinical state 95%, neurological sequelae 2%, death 3%. In the patients operated on for asymptomatic carotid stenosis the overall outcome was: previous clinical state 97%, death 3%. The legitimacy of carotid endarterectomy procedure is discussed in relation to some recent pertinent literature
Keywords: ARTERIAL-DISEASE/CAROTID ARTERY ATHEROMATOSIS/CAROTID ARTERY ENDARTERECTOMY/CAROTID ARTERY STENOSIS/CT/EEG/LOCAL-ANESTHESIA/MANAGEMENT/MORBIDITY/MORTALITY/NATURAL-HISTORY/OPERATIVE MANAGEMENT/OUTCOME/SURGERY
Benzel, E.C. and Hoppens, K.D. (1991), Factors Associated with Postoperative Hypertension Complicating Carotid Endarterectomy. Acta Neurochirurgica, 112 (1-2), 8-12.
Abstract: Blood pressure lability following carotid endarterectomy is a commonly observed phenomenon. Distinct hypertensive and hypotensive responses exist. Unlike postoperative hypotension, the etiology of postoperative hypertension remains unclear. In order to examine factors associated with hypertension following carotid endarterectomy, 100 carotid endarterectomies were examined retrospectively. The variables evaluated included pre- and postoperative blood pressure, age, sex, race, the use of an indwelling shunt, and complications. Postoperative hypertension (defined as systolic blood pressure greater than or equal to 200 mm Hg, diastolic blood pressure greater than 100 mm Hg, or any BP requiring intravenous infusion of antihypertensive agents for control), was observed in 35% of all patients. Postoperative hypertension was significantly associated with both preoperative systolic and diastolic blood pressure elevation, as well as the use of indwelling shunts. Increased age and race (black) were also associated with an increased incidence of postoperative hypertension. No correlation existed with respect to postoperative complications. In view of an observed lack of correlation with postoperative complications, a cautions and conservative therapeutic approach must be undertaken for postoperative hypertension. It is suggested that, perhaps, the utilization of trascutaneous doppler evaluations may be useful for assessing the clinical significance of postoperative hypertension
Keywords: CAROTID ENDARTERECTOMY/CEREBRAL HYPERPERFUSION/HEMORRHAGE/HYPOTENSION/INDWELLING SHUNT/NEUROLOGIC DEFICITS/POSTOPERATIVE HYPERTENSION/SHUNT/STROKE
Kruse, A., Cesarini, K.G., Bach, F.W. and Persson, L. (1991), Increases of Neuron-Specific Enolase, S-100 Protein, Creatine- Kinase and Creatine-Kinase Bb Isoenzyme in Csf Following Intraventricular Catheter Implantation. Acta Neurochirurgica, 110 (3-4), 106-109.
Abstract: In 15 patients without acute brain injury the concentrations of Neuron-specific Enolase (NSE), S-100 Protein (S-100), Creatine Kinase (CK), and Creatine Kinase BB isoenzyme (CK-BB) in ventricular cerebrospinal fluid (CSF) were measured immediately after lateral ventricle cannulation for diagnostic or treatment purposes. From patients who were treated with a shunt another CSF sample was obtained one week after shunt implantation by puncture of the antechamber of the valve. The CSF concentrations of NSE, S-100, CK and CK-BB after cannulation were found to be of the same order as found in patients with severe head injury, stroke or subarachnoid haemorrhage. One week after shunt implantation the concentrations of S-100, CK and CK-BB had returned to normal levels in almost all patients, while the NSE concentrations remained elevated. These findings indicate that the sampling procedure may result in contamination of CSF with NSE, S-100, CK and CK-BB and they should be taken into account in the prognostic evaluation of enzyme concentrations after brain injury
Keywords: CENTRAL NERVOUS-SYSTEM/CEREBROSPINAL FLUID/CEREBROSPINAL- FLUID/CREATINE KINASE ISOENZYMES/CSF/HUMAN-BRAIN/IMMUNOHISTOCHEMICAL LOCALIZATION/MARKERS/NEURON-SPECIFIC ENOLASE/S-100 PROTEIN/SEVERE HEAD-INJURY
Ogawa, A., Yoshimoto, T., Mizoi, K., Sugawara, T., Sakurai, Y. and Sato, H. (1991), Acute Revascularization for Progressing Stroke. Acta Neurochirurgica, 112 (3-4), 100-105.
Abstract: The effectiveness of acute stage vascular reconstruction in cases of progressing stroke is reported. The clinical material consists of 28 cases of progressing stroke in the anterior circulation upon which vascular reconstruction was performed. Following admission, brain protective substances (500 ml mannitol, 500 mg vitamin E, 500 mg phenytoin) and dextran, were administered to the patients, and induced hypertension was also performed. Changes in symptoms were then observed and vascular reconstruction was carried out in cases where symptoms progressed. The vascular lesion was on the internal carotid artery in 8 cases and on the middle cerebral artery in 20 cases. Complete disappearance of neurological symptoms was obtained in 12 cases, whereas only mild neurological symptoms remained but a return to normal social life was possible in 11 other cases. Symptoms remained in three cases and there were two fatalities. In a long-term follow-up study, there were no cases of aggravation of symptoms due to ischaemic stroke. Moreover, the reconstruction was judged as effective on the basis of cerebral blood flow and metabolism. We concluded that acute vascular reconstruction for progressing stroke under the administration of brain protective substances is effective in preventing the progression of neurological symptoms
Keywords: ACUTE STAGE VASCULAR OPERATION/BRAIN/BRAIN PROTECTING SUBSTANCE/BYPASS/CEREBRAL INFARCTION/ISCHEMIA/MANNITOL/PERFLUOROCHEMICALS/PROGRESSING STROKE/VITAMIN-E
Steiger, H.J. (1991), Outcome of Acute Supratentorial Cerebral Infarction in Patients Under 60 - Development of A Prognostic Grading System. Acta Neurochirurgica, 111 (3-4), 73-79.
Abstract: Thirty-five patients under the age of 60 were admitted to the Neurosurgical Department of the Inselspital with acute supratentorial ischaemic strokes between February 1985 and June 1990. The mean delay from the onset of the symptoms until emergency room admission was 10 hours. CT scan, Doppler sonography, and angiography were done routinely at the time of admission and CT was repeated 24 hours later. Initial treatment consisted of mannitol, low-molecular dextran and prednisolone. Intravenous nimodipine was added to the protocol in 1987. Intensive care including hyperventilation and intracranial pressure monitoring was instituted in cases of deteriorating level of consciousness and considerable oedema as visualized on the primary or repeat CT scan. Eight patients developing severe intracranial hypertension and/or unilateral mydriasis despite hyperventilation and osmotherapy underwent decompressive craniectomy. A total of 9 patients died in the acute stage, all but one due to a cerebral cause. At 6 months, only 6 patients were without significant neurological or neuropsychological deficits. Fourteen patients were moderately disabled and 6 were severely disabled. There were no vegetative survivors. A number of demographic, clinical and radiological variables were investigated for a possible prognostic significance. A grading scale was developed for each variable. Of the initial neurological deficits, degree of motor paralysis, gaze deviation, and decreased level of consciousness correlated with an unfavourable result. While the prognostic significance of each of these individual variables was only moderate, the combined score of these 3 variables correlated better with outcome (r = 0.62). More advanced age was found to correlate with a less favourable prognosis. The extension of the low-density area as visible on CT 24 hours after the event, was the single most significant prognostic factor (r = 0.63). The site of vascular pathology, as visualized on angiography, was less predictive. Arterial recanalisation, as demonstrated by Doppler sonography, was weakly associated with a more favourable prognosis. In conclusion, if the present preliminary data can be confirmed on a larger number of patients, the analysed variables allow assessment of the severity of hemispheric infarction for the purpose of therapeutic studies, however, the predictive value is not high enough to allow early therapeutic decisions for an individual patient