Biomedical subjects
Publications and source records attributed to J G Milton.
A 24-year-old woman with a left pontine hematoma showed marked asymmetry in the EEG of REM sleep, suggesting that a unilateral pontine lesion is sufficient to disrupt normal REM sleep EEG in the ipsilateral hemisphere. Other REM sleep characteristics (rapid eye movements, muscle atonia) were unaffected by this lesion.
Survival functions of the form p(t) = exp[-(lambda t) gamma], gamma greater than 0 can be generated by deterministic nonlinear, asymptotically stable (chaotic) dynamical systems. These systems thus provide an alternative to stochastic interpretations of failure time data. We use this approach to analyze cancer patient survival statistics. In this manner we are able to obtain fresh insights into the implications of negative and positive clinical trials.
The dependence of movement on visual information was compared for healthy individuals and Stage II-III patients with Parkinson's disease (PD). A time delay (0-1400 ms) was introduced into a visually guided motor tracking task which required the subject to maintain constant index finger position relative to a stationary baseline on an oscilloscope. For healthy individuals, delayed visual feedback induced complex oscillations in finger displacement. Similar results were obtained for four of eight patients with PD. However, oscillations were not induced in four of eight patients with PD because of reduced gain and/or a higher tremor amplitude at zero delay which obscured the tracking error. These results suggest that some patients with PD are able to utilize visual information for controlling tracking in this motor task in the same manner as healthy individuals.
Pupil cycling was produced using an electronic circuit so that the retina was illuminated in Maxwellian view only when pupil area exceeded an adjustable area threshold, Aref. The maximum (Amax) and minimum (Amin) amplitude of the oscillations varied linearly with Aref. These observations are described by a delay-differential equation. The Aref-dependent changes in Amax, Amin were used, respectively, to quantitate dilation and constriction. A comparison of the predicted and observed period of pupil cycling suggests that the latency times for light onset and offset are the same. Measurements of Amax, Amin provide a method for determining the average pupil light response.
This paper briefly reviews the role of mixed feedback, neural delays, and neural noise in the genesis of complex oscillations in neurological feedback systems. The results are concretely discussed within the context of recurrent inhibition in the mammalian hippocampus, and a hybrid version of the pupil light reflex with externally imposed electronic feedback.
Explore the source record for details and available documents.
Analogies are drawn between a physiologically relevant nonlinear delay-differential equation (DDE) model for the pupil light reflex and servo control analytic approaches. This DDE is shown to be consistent with the measured open loop transfer function and hence physiological insight can be obtained into the gain of the reflex and its properties. A Hopf bifurcation analysis of the DDE shows that a limit cycle oscillation in pupil area occurs when the first mode of the characteristic equation becomes unstable. Its period agrees well with experimental measurements. Beyond the point of instability onset, more modes become unstable corresponding to multiple encirclings of (-1, 0) on the Nyquist plot. These modes primarily influence the shape of the oscillation. Techniques from dynamical systems theory, e.g. bifurcation analysis, can augment servo control analytic methods for the study of oscillations produced by nonlinear neural feedback mechanisms.
Neurophysiological and anatomical observations are used to derive a non-linear delay-differential equation for the pupil light reflex with negative feedback. As the gain or the time delay in the reflex is increased, a supercritical Hopf bifurcation occurs from a stable fixed point to a stable limit cycle oscillation in pupil area. A Hopf bifurcation analysis is used to determine the conditions for instability and the period and amplitude of these oscillations. The more complex waveforms typical of the occurrence of higher order bifurcations were not seen in numerical simulations of the model. This model provides a general framework to study the different types of dynamical behaviors which can be produced by the pupil light reflex, e.g. edge-light pupil cycling.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We used an infrared videopupillometer combined with an electronic circuit that regulated the retinal light level as a function of pupil area to assess the regularity of pupil cycling in normal subjects and in patients with known abnormalities in the pupil light reflex pathways. The light stimulus was turned on whenever pupil area exceeded a preset value. Two types of abnormalities were observed for patients with demyelinative optic neuropathy: a failure of the pupil to cycle despite a preserved pupillary response to a single light pulse; and, for those patients in whom cycling was possible, a characteristic intermittent irregularity in the amplitude of pupil cycling. These abnormalities were not seen in normal subjects or in patients with ischemic optic neuropathy, surgical lesions involving the optic chiasm, Adie's syndrome, or Horner's syndrome.
Platelet shape was examined in freshly fixed whole blood, using phase contrast microscopy, from 7 patients post-myocardial infarction, 9 patients undergoing elective angiography for the investigation of angina, and 17 patients with stroke. Platelet shape was abnormal in 29/33 patients and in 20 of them the distribution of platelet shape did not resemble that produced by known platelet activators, by venipuncture techniques known to produce platelet activation, nor by shearing platelet-rich plasma. In particular, the proportion of spherical platelets is too high relative to the proportion of smooth discoid shaped platelets. Addition of platelet-poor plasma from a patient post-myocardial infarction to normal platelet-rich plasma did not reproduce the abnormality in platelet shape. In contrast, for patients post-myocardial infarction platelet shape was normal in platelet-rich plasma, but the platelets were hypersensitive to ADP-induced aggregation. Incubation of citrated whole blood at 37 degrees C resulted in an incomplete disappearance of the spherical platelets suggesting that the abnormal distribution of platelet shape consists of both a reversible and a more persistent abnormality. The reversible portion of the platelet shape abnormality seen in patients with stroke and coronary artery disease may be related to venipuncture-induced platelet activation; however, the nature of the persistent abnormality in platelet shape is presently unknown.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Platelet size on blood smear is compared with platelet size and shape in suspension (i.e., whole blood and citrated platelet-rich plasma [PRP]) for normal donors and 16 patients with hereditary "giant" platelet syndromes (HGPS), including Bernard-Soulier syndrome (BSS) (seven patients), Montreal platelet syndrome (MPS) (three patients), May-Hegglin anomaly (one patient) and Rafael platelet defect (one patient). In whole blood platelet shape is normal for HGPS, but in PRP for 10 of 16 patients with HGPS there is a decrease in the proportion of smooth, discoid-shaped platelets (discocytes [D]). The platelets of all patients with HGPS had abnormally large mean volume (VT) and increased size on peripheral blood smear. Furthermore, 12 of 16 patients with HGPS, including six of seven donors with BSS, had abnormally large discocytes. The measured size of HGPS shape-changed platelets was compared with the size predicted from the size of the D by assuming that the relationship between the size of shape-changed platelets and D was the same as observed for normal donors. In this manner it was shown that for all donors with BSS and MPS, the shape-changed platelets are disproportionately larger than the D. In contrast, in the remaining patients with HGPS the size of the shape-changed platelets was consistent with the size predicted from the D. Examination of VT for MPS as a function of time after addition of 10 mumol/L adenosine diphosphate to PRP revealed an abnormal time course, thereby pointing to an abnormality in the mechanisms that regulate platelet size during shape change. With the lone exceptions of BSS and MPS, the size of platelets on blood smear was well correlated with the total platelet plasma membrane surface area as measured by the osmotic spherocyte method. Our observations point to two distinct abnormalities in platelet size in HGPS: a disproportion between the size of D and "shape-changed" platelets, which may be related to an abnormal shape change and which is observed only for MPS and BSS, and an abnormal increase in platelet size on blood smear, which appears to reflect the increased amount of platelet plasma membrane in other HGPS platelets.
Geometries of platelets in citrated PRP obtained from normal donors (17) and donors (5) with a hereditary dominant giant platelet syndrome, herein referred to as "Montreal platelet syndrome" (MPS), are compared. The measured geometric axial ratio (rp = thickness/diameter) is used to classify platelet morphologies into three groups: discocytes (rp less than 0.5), disco-echinocytes (rp = 0.5 to 0.9), sphero-echinocytes (rp greater than 0.9). MPS discocytes are normal sized; however, MPS sphero-echinocytes and disco-echinocytes have mean volumes approximately two times larger than normal. It is demonstrated that these larger-than-normal sized MPS platelets can be produced directly from MPS discocytes by treatment with agents known to induce platelet shape change (adenosine diphosphate, thrombin, and incubation at 4 degrees C). Treatment of platelets obtained from normal donors which have been resuspended in MPS PPP and ADP or incubation at 4 degrees C causes the formation of normal-sized disco-echinocytes and sphero-echinocytes. The diameters of MPS disco-echinocytes are identical to the diameters of MPS platelets observed on peripheral blood smear, whereas those of MPS sphero-echinocytes are approximately 20% lower. It is suggested that the appearance of abnormally large platelets in MPS is related to a defect in the mechanism which regulates platelet size and shape during shape change.
Explore the source record for details and available documents.