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The histologic appearance of the lesion depends on its age Relatively recent lesions show a partial or complete destruction and loss of myelin throughout a zone formed by the con uence of many small, predominantly perivenous foci; the axons in the same region are relatively spared or less affected There is a variable but only slight degeneration of oligodendroglia, a variable neuroglial (astrocytic) reaction, and perivascular and para-adventitial in ltration with mononuclear cells and lymphocytes Later, large numbers of microglial phagocytes (macrophages) in ltrate the lesions, and astrocytes in and around the lesions increase in number and size Long-standing lesions, on the other hand, are composed of thickly matted, relatively acellular broglial tissue, with only occasional perivascular lymphocytes and macrophages; in such lesions, a few intact axis cylinders may still be found Sparing of axis cylinders (axons) prevents wallerian degeneration However, in old lesions with interruption of axons, there may be descending and ascending degeneration of long ber tracts in the spinal cord Partial remyelination is believed to take place on undamaged axons and to account for partially demyelinated shadow patches (Prineas and Connell) A few of the most severe older lesions will have undergone cavitation, indicating that the disease process has affected not only myelin and axons but also supporting tissues and blood vessels as well All gradations of histopathologic change between these two extremes may be found in lesions of diverse size, shape, and age, consistent with the extended clinical course This emphasis on the pathologic destruction of myelin obscures the central fact that the immune system effects this change, the myelin itself being normal in the structure and immune composition An insight into the complexity of the immunopathologic process can be appreciated in a recent microscopic analysis by Lucchinetti and colleagues (2000) of 83 autopsy and brain biopsy specimens from patients with MS They categorized several distinct histologic subgroups In most, the in ammatory response was distinguished by extensive perivenular deposition of immunoglobulin and complement, suggesting a role for a humoral pathogenesis In others, in ammation was present only at the periphery of plaques and the distinctive feature was a marked apoptosis of oligodendrocytes In yet another group, perhaps the end stage of the last one described, there was nearly complete loss of oligodendrocytes without apoptosis and an absence of remyelination Two features are of interest here First, each case demonstrated only one pattern of pathology, suggesting that perhaps different pathophysiologic processes operated in each patient Moreover, the last two histopathologic types were considered to represent a primary oligodendroglial degeneration A possible con rmation of the primary process in oligodendrocytes is the material from newly symptomatic lesions reported by Barnett and Prineas In 7 of 12 cases there were some lesions with oligodendrocyte apoptosis and microglial activation but without an in ammatory or macrophage response Aside from this novel idea regarding the oligodendrocytes, the overall implication is that the pathologic characteristics of the chronic progressive type of MS may differ from those of the typical relapsing type (see further on) However, further study will be required to determine whether these perspectives are valid or the differences simply re ect limited sampling, the age of the plaque, or the severity of an immune process At the moment, the authors regard observations of a primary role for oligodendrocyte destruction to be provisional and continue to conceptualize MS as an in ammatory-immune process that targets central myelin along the lines of the observations of Adams and Kubik in their earlier studies.

Before a variable can be used, it must be initialized in some way From what I ve seen, this rule seems to operate a little differently from a pure C# program and a hybrid ASPNET/C# one Generally, a definite assignment means that a variable needs to be initialized prior to use In some cases, you can just assign a data type such as

Figure 36-1 Multiple sclerosis T2-weighted MRIs demonstrating multiple plaques in the periventricular white matter (left), emanating radially from the corpus callosum ( Dawson ngers ) (middle), and cervical spinal cord (right) The radial orientation and periventricular location of cerebral lesions is typical of the disease

(1913)

private string myString;

Cruveilhier (circa 1835), in his original description of the disease, attributed it to suppression of sweat, and since that time there has been endless speculation about the etiology Many of the early theories appear ludicrous in the light of present-day concepts, and others are of mainly historical interest There is little point in enumerating them here; complete accounts are to be found in the reviews of DeJong (1970), Prineas (1970), R T Johnson (1978), and McDonald (1986)

In Chap 4, we truncatedthis result by excludingthe second-and higher-derivative tenns formula: and were thus left with a fbrward-difference

and then use the variable even though it has not been assigned a value For example, suppose you have the following ASPNET script:

Although the precise cause of MS remains undetermined, a number of epidemiologic facts have been clearly established and will eventually have to be incorporated in any etiologic hypothesis The disease has a prevalence of less than 1 per 100,000 in equatorial areas; 6 to 14 per 100,000 in the southern United States and southern Europe; and 30 to 80 per 100,000 in Canada, northern Europe, and the northern United States More recently, Mayr and colleagues reported an incidence of 8 and a prevalence of 177 cases per 100,000 in Olmstead County, MN; this prevalence has been stable for approximately 30 years A less well de ned gradient

+ o(h)

<%@ Page Language="C#" AutoEventWireup="true" CodeFile="DefiniteAssnaspxcs" Inherits="DefAssn" %> <!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 10 Transitional//EN" "http://wwww3org/TR/xhtml1/DTD/xhtml1-transitionaldtd"> <html xmlns="http://wwww3org/1999/xhtml"> <head runat="server"> <title>Definite assignment</title> </head> <body> <form id="form1" runat="server"> <div>

.

When running Perl via the command line, there are special treatments for some of the functions and operators we have already seen In general, these only affect Perl when you have called it with the -p and/or -i options For example:

(r9r4)