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Biomedical subjects

S Naimi

Publications and source records attributed to S Naimi.

At least 19 recordsLinked to original sources
PubMed1997

Maturation of fetal human neural xenografts in the adult rat brain.

Transplantation of human fetal neural cells has been used for several years as a treatment for Parkinson's disease. These therapeutic trials were based on a large number of rat allografts studies, and the species to species extrapolation appeared valid in many respects. One major difference between neurons of various species, however, is their rate of maturation; indeed, human neurons have been proven to grow much more slowly than rat neurons. This has been studied mostly, up to now, at the light microscope level. In an attempt to determine the fine structural correlates of this protracted development and to detail the schedule of morphogenesis and synaptogenesis, human fetal brain stem tissue (at 8 weeks of gestation) was transplanted into a previously lesioned brain area of immunosuppressed adult rats. Transplants, which were allowed to develop for 15 days to 3 months, were analyzed using the electron microscope. At 15 days, small cells containing a large nucleus were surrounded by wide extracellular spaces. At 1 month, grafted neurons displayed a thin rim of cytoplasm and few thin processes. At 2 months, extracellular spaces tended to diminish. Thin processes formed bundles and large processes extended from enlarged neurons. Major changes were observed at 3 months survival as the neuropile filled up with cells and processes and synaptogenesis began. Comparison with a similar ultrastructural study of thalamic rat allografts shows that human cells develop following a pattern similar to that in rat cells but that the duration of each maturation step is largely extended.

Animals↗
PubMed1997

Reasoning requirements for diagnosis of heart disease.

Over the past dozen years, the Heart Disease Program (HDP) has been developed to assist physicians in reasoning about cardiovascular disorders. Driven by several evaluations, the inference mechanism has progressed from a logic based model, to a Bayesian Probability Network (BPN) and finally a pseudo-Bayesian network with temporal and severity reasoning. Though aspects of cardiovascular reasoning are handled well by BPNs, temporal reasoning, homeostatic feedback mechanisms and effects of disease severities require additional inference strategies. This article discusses how these reasoning problems are handled, and deals with closely linked issues in building the user interface to collect detailed cardiovascular data and provide clear explanations of diagnoses.

Artificial Intelligence↗
PubMed1996

Ontogeny of human striatal DARPP-32 neurons in fetuses and following xenografting to the adult rat brain.

After a number of reports indicating positive clinical outcome of intrastriatal transplantation of fetal ventral mesencephalic tissue into patients with Parkinson's disease, the time may have come to consider the possibility of using this technique to treat patients with Huntington's disease. On the basis of the available literature, the Network of European CNS Transplantation and Restoration has established a program aiming at defining the optimal conditions for such clinical trials. The present study, conducted within this framework, pursued the goal of providing information concerning the period of striatal neuronal ontogeny in humans, taking into account the technical and legal requirements imposed by the clinical procedure of neural transplantation using human tissue. On this basis, it aimed at establishing a reliable dissecting method for the intrastriatal grafting of human fetal striatal neurons. The ontogeny of medium-spiny neurons within the developing striatum was first studied in a series of human fetal brains, 5 to 10 weeks postconception, using immunocytochemical detection of DARPP-32. Immunoreactive neurons were observed in fetuses at 7 weeks of age and older. They were mostly localized in clusters, packed in the lateral ganglionic eminence. Over a 2-week-long period, DARPP-32 neurons increased in number. Their morphology remained poorly differentiated, however, with small cell bodies, few branched dendrites, and variable intensity of immunostaining. Based on these findings, selective dissection of the lateral ganglionic eminence was carried out. This tissue was stereotaxically implanted into the striatum of immunosuppressed adult rats previously lesioned. Two months postgrafting, DARPP-32 neurons were observed as discrete patches, embedded within areas of essentially DARPP-32-negative tissue. Up to 2 months after grafting, neurons remained poorly differentiated in general, with only a few neurons exhibiting a dense immunoreactivity and long processes. These results indicate that striatal DARPP-32-immunoreactive neurons are present in the lateral ganglionic eminence in fetuses as soon as 7 weeks postconception. The striatal tissue can be dissected out and successfully transplanted. Within the grafts, neuronal differentiation appears to be a very long process, suggesting that many months might be necessary for these neurons to become functionally integrated into an adult host brain.

Animals↗
PubMed1996

Web interface for the Heart Disease Program.

The task of making a large complex diagnostic program available to a broad audience of physicians has become more feasible with the ubiquitous accessibility of the client-server architecture of the World Wide Web. This paper describes the design and implementation of a Web interface for the Heart Disease Program (HDP). The client-server architecture imposes a number of requirements on the program. The graphical capabilities of the Web enable a number of enhancements to the program but also cause some limitations. Our initial experience with physicians using the HDP through the Web interface has been positive and we are now conducting an evaluation of the HDP using this form of access.

Computer Communication Networks↗
PubMed1994

Summarization of complex causal diagnostic hypotheses.

The Heart Disease Program produces detailed causal diagnostic hypotheses for patients with cardiovascular diseases. This poster discusses our experience with summarizing these hypotheses for the physician. The basic approach is to merge the nodes of the structure indicating causal mechanism into the more important nodes. Analysis of the results shows that to generate effective summaries the identification of syndromes is very important, the definitions of the labels need to be carefully enforced, the causality of diseases should be supported by evidence and not just probability, and the sense of causal order must be carefully preserved.

Heart Diseases↗
PubMed1992

Development of a knowledge base for diagnostic reasoning in cardiology.

This paper reports on a formative evaluation of the diagnostic capabilities of the Heart Failure Program, which uses a probability network and a heuristic hypothesis generator. Using 242 cardiac cases collected from discharge summaries at a tertiary care hospital, we compared the diagnoses of the program to diagnoses collected from cardiologists using the same information as was available to the program. With some adjustments to the knowledge base, the Heart Failure Program produces appropriate diagnoses about 90% of the time on this training set. The main reasons for the inappropriate diagnoses of the remaining 10% include inadequate reasoning with temporal relations between cause and effect, severity relations, and independence of acute and chronic diseases.

Artificial Intelligence↗
PubMed1988

Prolongation of the conduction time of early premature beats: a marker of ventricular action potential duration.

The conduction time of premature ventricular complexes, which are generally quite constant throughout late diastole, abruptly prolongs during repolarization as the refractory period of the ventricle is approached (conduction time breakpoint). The relationship between the conduction time breakpoint and the recovery properties of the ventricle was examined by relating the conduction time of premature ventricular complexes to the effective refractory period and the monophasic action potential derived from the ventricular suction electrode signal. In five anesthetized dogs during ventricular drive (cathode; 2.5 Hz; three times diastolic threshold), effective refractory period and conduction times of premature ventricular complexes were derived from computerized strength-interval curves. The recovery properties of the ventricle were altered by infusion of norepinephrine, calcium, and quinidine and by cooling (29 degrees to 34 degrees C). In these circumstances, the moment of conduction time breakpoint changes correlated well (r = 0.93) with the end of the negative slope of the ventricular suction electrode signal, which suggests that the conduction time breakpoint may be an indirect marker of the ventricular action potential duration. In seven additional dogs the interval between the effective refractory period and the conduction time breakpoint, which defines the relative refractory period, was increased by 5 to 8 minutes of ischemia (coincident with height of ventricular vulnerability) and was reversed by procainamide. Procainamide is known to diminish spontaneous and induced ventricular arrhythmias by reducing the disparity between the effective refractory period and the action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1986

The cardiointegram: detection of coronary artery disease in males with chest pain and a normal resting electrocardiogram.

The cardiointegram is a non-invasive technique for the analysis of the electrical signals of the heart obtained by a transformation of the voltage vs. time format by a series of integrations. This multicenter study compares the results of the cardiointegram with coronary arteriography in 140 male patients with chest pain and a normal resting electrocardiogram. The cardiointegram was determined on two resting complexes of Leads I, II, V4, V5 and V6 and called abnormal if greater than or equal to four of ten complexes were abnormal, i.e., fell outside of a previously determined template of normality. The sensitivity was 73% and specificity was 78% for the diagnosis of occlusive coronary artery disease. When greater than or equal to five of ten abnormal complexes were used as the cut-off for an abnormal test and "equivocal" results (four of ten abnormal, n = 18) were excluded from analysis there was a sensitivity of 69% and specificity of 88%. Thirty-seven of 38 patients (97%) with an abnormal cardiointegram and a positive exercise stress test had coronary artery disease. Thus, the cardiointegram appears to be a useful non-invasive test for the detection of coronary artery disease in males with chest pain and a normal resting electrocardiogram in whom the diagnosis of coronary artery disease is being considered.

Angiocardiography↗
PubMed1982

Regression of myocardial hypertrophy: electrocardiographic-echocardiographic correlations after aortic valve replacement in patients with chronic aortic regurgitation.

Serial electrocardiographic and echocardiographic left ventricular (LV) studies were performed in 21 patients before and after aortic valve replacement (AVR) for chronic aortic regurgitation. Changes in voltage (SV1 + RV5-6) after AVR were assessed and evaluated relative to changes in LV mass. Muscle cross-sectional area (CSA) derived from echocardiographic dimension and wall thickness data was used as an index of LV muscle mass (LV hypertrophy greater than 10 cm2/m2). In 15 patients, voltage was reduced after AVR: Seven had normal voltage (48 +/- 17 mm to 25 +/- 6 mm, p less than 0.005) and eight still had increased voltage (61 +/- 17 mm to 40 +/- 4 mm, p less than 0.01). Patients with normal voltage had complete regression of hypertrophy by echocardiography (CSA decreased from 13 +/- 3 cm2/m2 to 9 +/- 1 cm2/m2, p less than 0.025), while those who had persistently increased voltage had incomplete regression (15 +/- 2 cm2/m2, p less than 0.001). Reduction in voltage generally occurred in the first 6 months after AVR. Three patients with unchanged voltage had evidence of paraprosthetic regurgitation and minimal change in CSA. Three other patients with voltage had evidence of paraprosthetic regurgitation and minimal change in CSA. Three other patients with persistent LV enlargement without paraprosthetic regurgitation had a severe intraventricular conduction delay. Data from 59 electrocardiographic-echocardiographic studies before and after AVR revealed a strong correlation (r = 0.81) between voltage and muscle CSA. After surgical correction of chronic aortic regurgitation, regression of LV hypertrophy can be assessed by serial electrocardiographic studies. These ECG data identify patients with complete, incomplete or no regression of LV hypertrophy.

Aortic Valve↗
PubMed1979

The rapid generation of strength-interval curves under computer control.

A system was developed to allow for the rapid evaluation of myocardial excitability and conduction in canine preparations. The stimulus strength required to excite a propagated response, as a function of time since the last depolarization, can be summarized by a strength--interval curve. Our system generates strength-interval curves under computer control with high accuracy and efficiciency. The conduction time of each ventricular response is also determined. At a heart rate of 2.5 Hz, the average time for curve generation is 94 s, an efficiency which is 85% of the theoretical maximum. This system has been employed in over 120 dogs to generate strength--interval curves during rapidly changing periods of myocardial ischemia and during interventions with various drugs.

Animals↗
PubMed1979

Time course of changes in ventricular excitability and conduction during myocardial ischemia and reperfusion in the dog: effect of lidocaine.

Strength-interval curves and conduction times were determined in anesthetized dogs during and following myocardial ischemia using a computerized system capable of determining a 5 point strength-interval curve with conduction times within 20 seconds. At the peak incidence of ligation arrhythmias (5 minutes of ischemia), the falling limb of the strength-interval curve was shifted to the left and conduction time was prolonged, while at 15 minutes of ischemia, the strength-interval was shifted upward and conduction times had returned toward control. Lidocaine enhanced the upward shift of the strength-interval curve, contributing to the electrical stability of the myocardium during this phase of ischemia. During the first minute following abrupt reperfusion of the ischemic zone, there was a slight downward shift of the early part of the strength-interval curve, and conduction times tended to be shorter than control. Lidocaine enhanced the electrophysiological alterations following abrupt reperfusion; that is, it reduced excitation thresholds and increased the tendency to superconductivity. Thus, lidocaine enhanced electrical stability during acute ischemia but tended to exaggerate electrophysiologic defects observed during abrupt reperfusion.

Animals↗
PubMed1978

Sequential unipolar strength-interval curves and conduction times during myocardial ischemia and reperfusion in the dog.

Computerized techniques were employed to generate alternating anodal and cathodal or sequential anodal strength-interval curves during and following 15-minute coronary artery ligations in 14 anesthetized dogs. The right atrium was paced at 2.5 Hz, and unipolar ventricular strength-interval curves with simultaneous conduction times were recorded every 45-120 seconds during ischemia and reperfusion. Within 1--2 minutes of ligation, anodal midcurve and late diastolic thresholds fell sharply, and cathodal thresholds fell slightly or changed little. After 5 minutes of ischemia, anodal thresholds remained low, cathodal thresholds rose, and conduction times increased. At 10--15 minutes of ligation, if the ischemic zone was small, anodal thresholds were low, often approaching cathodal values, and conduction returned toward control values. When the ischemic zone was large, unipolar thresholds and conduction times increased late during the ligation period. Throughout the course of ischemia, the falling limb of the strength-interval curve shifted progressively to the left indicating shorter refractory periods. Following abrupt reperfusion, anodal phase 3 dips promptly reappeared; refractory periods returned toward control, and supernormal conduction was noted. By 3--5 minutes of reperfusion, the falling limb of the strength-interval curve had shifted to the right of control and conduction times increased. Thus, vulnerability to arrhythmias during early ischemia (i.e., 5 minutes) is characterized by low anodal midcurves and late diastolic thresholds, short refractory periods, and slow conduction. During the first minute of reperfusion, anodal excitability is increased during the early dip and conduction times are supernormal. Increases in anodal excitability correlate better with the peak incidence of early ligation and reperfusion arrhythmias than do changes in cathodal excitability.

Animals↗
PubMed1977

Dispersion of effective refractory period during abrupt reperfusion of ischemic myocardium in dogs.

Dispersion of the effective refractory period was measured in anesthetized dogs using a computerized system and bipolar epicardial electrodes or, alternatively, transmural plunge electrodes. Measurements were made at 1 minute intervals during short (5 minute) and long (15 minute) periods of coronary arterial ligation and for 3 to 5 minutes after release of the ligatures. Both transepicardial and transmural temporal dispersion of refractoriness correlated well with the increased vulnerability to spontaneous ventricular fibrillation during short periods of ligation and the relative electrical stability observed toward the end of the longer periods of ligation. During reperfusion, transmural dispersion increased somewhat after ligature release in the longer-term experiments but the increase did not appear adequate to explain the associated large incidence of spontaneous arrhythmias after release. Effective refractory periods measured at one nonischemic and five ischemic electrode sites at intervals as short as 20 seconds revealed abrupt shortening of the refractory period at all ischemic sites during the 1st minute of reperfusion, resulting in a large but short-lived electrical gradient between the ischemic and nonischemic myocardium. This increased dispersion between the ischemic and nonischemic myocardium occurred at a time of maximal vulnerability to reperfusion arrhythmias. However, this increased dispersion was greater after the 5 minute than after the 15 minute periods of ligation and thus does not fully explain the greater incidence of reperfusion arrhythmias after ligature release in the longer-term studies. Although arrhythmias of acute ischemia are associated with increased dispersion of refractoriness within theischemic segment and reperfusion arrhythmias with dispersion between ischemic and nonischemic segments, other electrophysiologic alterations probably play an important role in the genesis of the arrhythmias of reperfusion.

Animals↗