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M W Cooper

Publications and source records attributed to M W Cooper.

8 recordsLinked to original sources

A real-time analysis of growth cone-target cell interactions during the formation of stable contacts between hippocampal neurons in culture.

Mechanisms of cell-cell recognition and structural changes of growth cones (g.c.) and target membranes during contact formation are poorly understood. To examine these issues, we obtained a high magnification, real-time record of stable contact formation in cultured cells from the hippocampal CA1 area in the newborn rat. We used differential interference contrast (DIC) optics coupled to a video microscope for periods of over 24 h of continuous time-lapse recording. Our goal was to observe the sequential changes exhibited by afferent and target cells as they form a stable contact. Understanding the process of how stable contacts are made is important because such contacts are the first step in synapse formation. Four principal observations emerged from our study: (1) The target cell was receptive to a contact on a specific patch on its surface defined by the presence of lamellae and filopodia. This specific patch (named target site) was invariably present on the target cell surface before the time the growth cone arrived. (2) Stable adhesion between filopodia on the two cells initiated events leading to cell-cell contact formation. Specifically, the remaining filopodia on the growth cone and target cell were redirected toward the adhering filopodia, and the growth cone size decreased dramatically. (3) The axonal process then grew at a significantly accelerated rate (up to 50 times its baseline growth rate). (4) In addition, a number of observations were obtained on axonal turns towards the target cell, induction of target sites, and architectural remodelling of cells after the formation of a new contact. Our findings indicate that in this neuronal system, filopodia are the means used by cells to interact at stages prior to and during contact formation. We speculate that the molecules involved in cell recognition and the machinery that initiates contact formation are embedded in the fine structure of filopodia. Finally, our results provide possible clues as to some of the stages that may be involved in synapse formation in the mammalian central nervous system.

Animals

Should physicians be bayesian agents?

Because physicians use scientific inference for the generalizations of individual observations and the application of general knowledge to particular situations, the Bayesian probability solution to the problem of induction has been proposed and frequently utilized. Several problems with the Bayesian approach are introduced and discussed. These include: subjectivity, the favoring of a weak hypothesis, the problem of the false hypothesis, the old evidence/new theory problem and the observation that physicians are not currently Bayesians. To the complaint that the prior probability is subjective, Bayesians reply that there will be ultimate convergence, but the rebuttal to this is that there will not be uniform convergence. Secondly, since the Bayesian scheme favors a weak hypothesis, theories turn out to be a gratuitous risk. The problem with the false hypothesis comes out in the denominator of the theorem, revealing that a factor which is not a theory at all is being considered in the reasoning. On the old evidence/new theory problem old evidence cannot confirm a new theory so that the posterior probability will equal the prior probability. Finally, empiric studies have shown that current physicians are not Bayesians. But on consideration of Bayesian inference as a system of inference, it can be reasoned that physicians should be Bayesians. However, the problem of physicians' and patients' own subjectivity continue to plague this system of medical decision making.

Bayes Theorem

Comparison of ionic and non-ionic contrast agents in cardiac catheterization: the effects of ventriculography and coronary arteriography on hemodynamics, electrocardiography, and serum creatinine.

We compared two nonionic contrast agents (ioxaglate and iohexol) with an ionic agent (Renografin-76) on the effects of ventriculography and coronary arteriography on the hemodynamics, electrocardiography, and serum creatinine in one hundred consecutive patients. Patients were randomized to nonionic or ionic groups and were further evaluated regarding the effect of fluid loading prior to catheterization. The ionic agent more often produced subjective reactions (rash, nausea/vomiting). Following ventriculography, both ionic and non-ionic agents produced an increase in left ventricular end diastolic pressure and this effect was undetermined by fluid loading. Nonionic agents decreased aortic diastolic pressure following ventriculography and this effect was unaltered by fluid loading. In contrast, the ionic agent produced profound hemodynamic changes (drop in both systolic and diastolic pressures) following coronary arteriography and these effects were blunted by prior fluid loading. The ionic agent produced significantly greater heart rate slowing and prolongation of the QT interval than the nonionic agents, suggesting that the latter are potentially less arrhythmogenic. Comparing the two non-ionic agents, we found that both decreased aortic diastolic pressure and increased left ventricular end diastolic pressure following ventriculography. Iohexol produced greater heart rate slowing than did ioxaglate, though the increase was minor compared to the ionic agent. Neither nonionic agent appeared to significantly affect serum creatinine. In conclusion, the two nonionic agents appeared to offer significant advantages over the ionic agent in ventriculography and coronary arteriography.

Contrast Media

Electrocardiography and postextrasystolic potentiation: utilization of the two methods to predict postrevascularization segmental myocardial function.

We previously reported that postextrasystolic potentiation (PESP) is a useful predictor of changes in systolic wall function (SWF) following coronary revascularization. In the current study we analyzed ECG changes related to corresponding myocardial segments to determine their correlation with PESP and SWF. We found: (1) The PESP response in a jeopardized segment was a valid predictor of improved SWF even when Q waves, ST-segment changes, or T-wave changes were present. (2) However, when Q waves were present in two or more of the corresponding leads, positive PESP was less likely to be observed. (3) Thus Q waves in two leads predicted the least postrevascularization improvement. (4) Segments with no corresponding Q-wave postrevascularization usually improved SWF. (5) Furthermore, a continuum of responsiveness to PESP was found, ranging from T-wave changes, ST-segment changes to Q-wave changes, indicating dissociation between electrical and mechanical events. In conclusion, the ECG together with PESP provide good predictive information relative to the efficacy of revascularization. PESP is a more valuable predictive indicator. ECG alone may be of value in that the occurrence of Q waves in two or more corresponding leads predicts a low probability of improved SWF. Further studies are indicated to investigate the dissociation between electrical and mechanical events.

Blood Pressure

"Isolength" postextrasystolic potentiation as a predictor of functional restoration following surgical revascularization for myocardial ischemia.

A previously developed method of programmed postextrasystolic potentiation (PESP) was assessed in eight patients with medically refractory unstable angina, as a predictor of functional restoration resulting from surgical revascularization. Prior to coronary arteriography, left ventricular segmental wall motion was determined during ventricular pacing and the first postextrasystolic beat following an extrasystole. The postextrasystole was induced at an interval calculated to occur at a time where ventricular preload was identical to the regular paced beat (isolength interval). The left ventricular wall was divided into six segments, each subscribing one area of the ventriculogram, and correction for rotation during systole was made. Of 48 segments, 21 were considered "jeopardized," due to greater than 70% reduction in cross-sectional lumen of the serving coronary arteries. Fifteen of these 21 responded to PESP, increasing their segmental area ejection fraction from 44 +/- 5 (paced "normal" beat) to 56 +/- 6 (postextrasystolic beat) (p less than 0.05). Following surgical revascularization, these segments showed an improvement in their baseline area ejection fraction from 44 +/- 6 to 58 +/- 5 (p less than 0.05). Six jeopardized segments that failed to respond to PESP prior to revascularization showed functional deterioration after revascularization. The 27 non-jeopardized segments (which were not revascularized) also showed functional improvement, suggesting improved collateral flow. This study demonstrates that isolength postextrasystolic potentiation obtained with a standardized pacing protocol may be used to predict the potential for improvement in cardiac function following surgical revascularization. Our results also show that lack of PESP predicts loss of left ventricular myocardial function following revascularization.

Aged

Postextrasystolic potentiation: analysis of methods of induction.

Studies were conducted in 15 patients with coronary artery disease to determine if the type of pacing used to induce an extrasystole had a bearing on subsequent postextrasystolic potentiation (PESP) and if the fact that these were evaluated in jeopardized or nonjeopardized portions of the ventricle altered the ability to assess PESP. Two types of pacing were used. In the first group, all beats in the test sequence (basic heart rate, extrasystole, and postextrasystole) were delivered from a programmed external pacemaker. This group was termed the "all-paced" (AP) group, and the postextrasystole was introduced before a compensatory pause could occur, so that loading conditions within the ventricle at the last regular beat and after the extrasystole were not different. In the second group, the extrasystole was coupled to the sensed intrinsic heart rate of the patient, and the postextrasystole was allowed to occur spontaneously. This group was termed the "sensed-paced" (SP) group. Despite differences in basic heart rates and postextrasystolic intervals between the two groups, comparable results were obtained with the two techniques. However, the postextrasystole in the SP group occurred much earlier than expected, probably due to intrinsic cardioacceleration during ventriculography. The net result was that loading conditions in this group before and after the extrasystole were also not different from each other. Results from the pacing techniques were not influenced by whether they were obtained from jeopardized or nonjeopardized segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization

Postextrasystolic potentiation: regional wall motion before and after revascularization.

We evaluated the augmentation of contractility which follows an extrasystole (postextrasystolic potentiation: PESP) in patients before and after coronary revascularization surgery for angina pectoris. PESP was induced by methods which result in essentially identical loading conditions of the ventricle for the beat before the extrasystole and the beat after the extrasystole. We evaluated regional ventricular function before and after revascularization in "jeopardized" segments (supplied by a coronary vessel with significant coronary disease) and "nonjeopardized" segments (supplied by a vessel without significant disease). All coronary lesions were proximal to all three anterior or all posterior segments. Those jeopardized segments with patent grafts which had augmented with PESP improved their baseline function following revascularization. Conversely, those jeopardized segments which failed to augment with PESP decreased their basic function following revascularization. Those segments in which the grafts were occluded failed to augment with PESP after attempted revascularization. Perioperative myocardial infarction resulted in a drop in ejection fraction and a failure to augment with PESP. The nonjeopardized segments responded to PESP similarly to the ischemic augmenting segments. The results of this study suggest that PESP does detect ventricular segments which will improve basic function following revascularization. Those segments which fail to augment with PESP are most likely more ischemic than the augmenting segments, will not improve, and may even decrease function following revascularization.

Angina Pectoris