Lesions permanent

Signs and Symptoms Symptoms are acute and include fever, headache, encephalitis, vesicular skin lesions at site of the exposure, and variable neurological patterns. Involvement of the respiratory center and death usually occurs in 1-21 days after onset of symptoms. Survivors usually have considerable residual disability. May produce severe permanent neurologic impairment requiring lifelong institutionalization. 

Lesions may take months to heal completely, and fibrosis associated with healing may lead to permanent scarring. 

Since the early 1980s, much effort has focused on animal models of acute and chronic neurodegeneration in search of therapeutics for stroke. Neuronal cell death follows strokes, acute ischemic insults, and chronic neurodegeneration, such as Parkinson s disease, Alzheimer s disease (AD), epilepsy, and Huntington s disease. Up to 80% of all strokes result from focal infarcts and ischemia in the middle cerebral artery (MCA), so the commonly used animal models for neuroprotection are produced by temporary or permanent occlusion of the MCA.5 Lesions of the MCA include occlusion by electrocoagulation, intraluminal monofilaments, photochemical effects, thrombosis, and endothelin-1, but all of these models necessitate studying reperfusion events and validating MCA occlusion by behavioral assessments. 

Areas related to the evaluation of the adversity of an effect are reversibility and irreversibility and adaptation to an exposure. Irreversible effects are always of great concern. Reversible effects may also be of great concern depending on the nature of the effect and on the setting in which they occur. It cannot be mled out that a permanent lesion may have occurred even if the overt effect is transient. Eurthermore, when there is a more or less continuous exposure to a substance, the question of reversibility is not relevant because adaptation systems will be counteracted by new insults. In many cases it is not possible to draw any conclusion on whether an effect is reversible or not as such experimental data are rare, and all significant health effects that can impair function, both reversible and irreversible, should therefore be considered in the hazard assessment. 

With severe intoxication, lesions of the anterior horn cells and the pyramidal tracts may also occur. Muscular weakness may increase over a period of several weeks or months recovery may take months or years and in 25-30% of cases, permanent residual effects remain, usually confined to the lower limbs. Gait impairment, characterized by high steps and footdrop and permanent in some, was called Jake Walk. ... 

Of the long-term complications of wartime exposure to mustard gas, perhaps the best documented and one of the most serious is recurring corneal ulcers, with eventual opacification and blindness. No exact figures are available for predicting the eventual development of such long-term corneal lesions, but it has been reported that a Ct of 100 mg min/m will cause acute blindness for 24-48 h.20 Permanent blindness typically occurred about 14 yr... 

The concept of toxicity is an important one it involves a damaging, noxious, or deleterious effect on the whole or part of a living system, which may or may not be reversible. The toxic response may be a transient biochemical or pharmacological change or a permanent pathological lesion. The effect of a toxic substance on an organism may be immediate, as with a pharmacodynamic response such as a hypotensive effect, or delayed, as in the development of a tumor. 

The best way to illustrate the importance of DNA repair is to consider the effects of unrepaired DNA damage (a lesion). The most serious outcome is a change in the base sequence of the DNA, which, if replicated and transmitted to future cell generations, becomes permanent. A permanent change in the nucleotide sequence of DNA is called a mutation. Mutations can involve the replacement of one base pair with another (substitution mutation) or the addition or deletion of one or more base pairs (insertion or deletion mutations). If the mutation affects nonessential DNA or if it has a negligible... 

Fig. 11.1. Photograph of the distal surface of an extracted permanent human premolar containing an early carious lesion (white spot)...

The randomized controlled clinical trials performed by Freis and his colleagues at the Veterans Administration Hospitals have provided some of the first solid evidence that moderate permanent hypertension has an improved prognosis when actively treated by sodium depletion (hydrochlorothiazide), by interruption of the sympathetic nervous system (reserpine) and with a vasodilator (hydralazine) (262). In parallel, the beneficial effects of this triple therapy were demonstrated in spontaneously hypertensive rats by the spectacular prevention and cure of their cardiac, vascular, and renal lesions (263). 

Much debate exists over the accuracy of the acute DWI lesion identifying the ischaemic core, that is, tissue that is irreversibly damaged. There is no doubt that diffusion lesions may be partially reversed with early reperfusion. This has been demonstrated in both animal and human stroke (Chalela et al. 2003 Kidwell et al. 2000 Li et al. 1999,2000). However, in humans these lesion reversals in most instances are only minor or partial, and are quite often not permanent. Indeed, in our thrombolytic series, less than 5% of patients had what would be considered any significant reduction in ischaemic lesion volume between the pre-treatment DWI and outcome T2-weighted... 

Fig.4.3a-f. The phenomenon of infarct maturation is shown as macroscopic appearance on hematoxylin-eosin stained coronal brain sections. Right permanent middle cerebral artery occlusion was performed in rats and histology obtained between 3 h and 7 days. Note the sparse changes at 3 h and lesion shrinkage at 7 days. [Reproduced with permission from Garcia et al. (1993)]... 

Fig. 4.8. Lesion development in permanent middle cerebral artery (MCA) occlusion in a rat measured by repeated MR diffusion-weighted imaging (DWI). Left column Control condition pre-occlusion in coronal slices from posterior (top) to anterior (bottom). The arrow marks the timepoint of occlusion. Images shown in columns 2 to 7 are DWI (subtraction images) measured 30 to 330 min post-occlusion. Note the lesion growth and the increase in signal intensity within the lesion. (Courtesy Dr. M. Hoehn, Cologne)...

Fig. 4.9. Lesion development in stroke models of permanent focal ischemia (PMCAo) visualized by histology (left) and diffusion-weighted (DW) imaging. [Adapted from Garcia et al. (1993) and Brinker et al. (1999)]...

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