Lael Stone

MRI studies of multiple sclerosis: Implications for the natural history of the disease and for monitoring effectiveness of experimental therapies:

The use of magnetic resonance imaging (MRI) in multiple sclerosis (MS) has increased in our understanding of the natural history of the disease course and has provided and important tool for the analysis of new experimental therapies. Studies using MRI as well as pathological studies of MS indicate that the first event in the development of a new MS lesion as seen on T2 weighted images is disruption of the blood brain barrier (BBBD) which can be demonstrated by areas of increased signal on T1 weighted images done after the administration of gadolinium DTPA When GdDTPA enhanced MRIs are used to monitor disease activity in patients with mild relapsing remitting MS, a considerable degree of disease activity is observed in clinically stable patients. These findings indicate that MS is an active and progressive disease in most patients even during the earliest phases of the disease and before significant clinical disability has occurred. MRI is also an important tool in evaluating new therapies. Using simple baseline vs treatment designs evidence for an effect of a new treatment on MRI parameters such as Gd-DTPA enhanced measure of BBBD can be achieved using a small study cohort and over a short duration. Together these advances should lead to more rapid progress in the understanding of MS and in identifying new treatments.

Clinical characteristics of outpatients with chronic major depression

A cross-sectional evaluation of 243 unipolar, nonpsychotic outpatients with major depression was conducted. All subjects were diagnosed by RDC with SADS-L structured interviews. Diagnoses included RDC primary/secondary, RDC endogenous/nonendogenous and Winokurs family-history subtypes. Symptom severity was assessed by the 17-item Hamilton Rating Scale for Depression. Chronic depression was defined as the current episode of major depression lasting at least 2 years, corresponding to DSM-III-R and -IV criteria. Patients with chronic depression (n = 64) were compared with those with nonchronic depression (n = 179). Chronicity was not related to gender, symptom severity, prior length of illness, age at onset of illness, RDC endogenous/nonendogenous, RDC primary/secondary or Winokurs family-history subtypes. Those with chronic depression were older and had fewer major depressive episodes than the nonchronic group. That the chronic group had fewer total episodes of depression than the nonchronic group, but a similar age at onset, is consistent with the notion that patients in a current chronic episode have characteristically longer depressive episodes throughout the course of their illness. Those with chronic episodes may be subject to psychological, biological and/or sociocultural factors that preclude an earlier episode remission for these individuals.

EXPRESSION PATTERN OF ACTIVATION AND ADHESION MOLECULES ON PERIPHERAL BLOOD CD4+ T-LYMPHOCYTES IN RELAPSING-REMITTING MULTIPLE SCLEROSIS PATIENTS : A SERIAL ANALYSIS

We studied the expression of various cell surface molecules (CD25, CD28, CD29, CD45RO, CD56, LFA-1, VLA-4) on peripheral blood CD4+ T-cells in 6 relapsing-remitting multiple sclerosis (RR-MS) patients. Furthermore, changes in the expression pattern of these surface markers during intervals of increased disease activity, which was measured by gadolinium (Gd-DTPA) magnetic resonance imaging (MRI) were examined. Although several patients showed signs of increased disease activity during the observation period, this was not paralleled by a relevant change in the expression of these activation and adhesion molecules.

Evaluation of magnetic resonance imaging sensitivity in patients with relapsing remitting multiple sclerosis: Baseline versus betaseron treatment trials

From the 1Laboratory of Diagnostic Radiology Research, Office of Intramural Research, and 2Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD; and 3Hospital of the University of Pennsylvania, Philadelphia, PA. Address reprint requests to J. A. Frank, MD, OD OIR LDRR, Bldg. 10, Rm. B1N256, 10 Center Dr., MSC 1074, Bethesda, MD 20854-1074.

Growth-guided shape recovery

A central problem in computer vision is to detect, delineate (segment) and recognize objects in an image. One reason why this is difficult is that very little information specific to given types of objects is used during segmentation. Making use of information about an objects shape -- in particular, about how it grows -- should facilitate and improve the segmentation of that object. We introduce a 2D discrete growth model for shapes on a Cartesian grid, based on notions related to biological growth. By growth is meant an accretionary process occurring at the boundary of the shape. We introduce a new type of deterministic growth model based on the notion of time delay. Associating a delay with each direction defines a time delay kernel (TDK); such kernels produce classes of convex octagons, and sequences of TDKs can give rise to arbitrary convex polygons. We show that growth in a stochastic environment of facilitators and inhibitors, which decrease or increase the time delays respectively, is a plausible analog for biological growth processes. As an example, we present results which suggest that simple periodic growth processes in an environment describe the gross morphology of multiple sclerosis lesions at the scale afforded by magnetic resonance images.