Pathological Deviations

The leukocyte response is inadequate in a great number of clinical conditions. Most of the disorders described have been associated with an increased susceptibility to infections. However, the biochemical or molecular level of the various defects have not been clearly established, except for some genetically determined deficiencies. A few examples of neutrophil abnormalities will be given in the two subsequent sections, but for a more complete insight into PMN phagocytic disorders, general reviews and monographs are available (K2, B2, Wl, W3, K3). 

Phagocytic dysfunction is known to occur during the course of a large number of acquired conditions, but the relationship between the altered function of the PMN and the clinical state of the patient is difficult to find out in many cases. 

PMN from patients with alcoholic cirrhosis were shown to have defec- 

PMN of anemic subjects with iron deficiency were capable of producing normal quantities of H2O2 under resting and phagocytosing condi- 

PMN function was studied in children suffering from recurrent otitis media (Gl) A depressed chemotactic response in 17.5% of 87 patients, depressed bactericidal activity in 23% of 30 patients, and depressed chemiluminescence in 15.8% of 19 patients were found. However, it is not known if PMN dysfunction is a consequence or a cause of the clinical problem. 

---

Pathological deviations include an absence of junctional folds, partial innervation (folds without an overlying nerve terminal), and vacuolated mitochondria. Assessing more subtle defects, such as changes in vesicle number, requires a statistical analysis on many junctions. 

Clinical picture. It is manifested by the following syndromes a) irritative - catarrhal expressions on the contact mucosa b) renotoxic - by oligo- or anuria, pathological deviations in urine indications and manifestation of kidney insufficiency c) cerebro-toxic - manifested by convulsions, delirious fits, sometimes by consciousness derangement, gradual fall into neurotoxic degradation and dementia events. 

Clinical manifestation. It includes several syndromes a) pulmotoxic and irritative syndrome - expressed by catarrhal changes on the contact mucosa and respiratory tract, toxic pulmonary oedema b) hemotoxic syndrome - expressed by severe hemolysis of different degrees, in the severe forms - hemolytic shock and anaemia c) hepatal syndrome - characterised by subicterus or icterus, increased liver and bilirubinaemia d) renal syndrome - by oliguria or anuria, pathological deviations in the urine and acute kidney insufficiency. In the extremely severe forms consciousness is disordered. Laboratory blood and urine chemical tests show evidence of phenol metabolites, data for blood damage (increased values of free hemoglobin, reduced number of erythrocytes), positive liver tests etc. 

In addition, we studied the acute toxicity of the total ethanolic extract TE2 and its main component esculin (1) and found that applied p.o. to white mice and white Wistar rats in doses from 50 to 8000 mg/kg they were practically non-toxic. No lethality was observed up to 21 aay and with the highest doses used. No significant changes were found both in the behavior and the reflexes of the animals. No pathological deviations from the physiological values were found in all hematological and clinical -chemical indices studied. 

There are other fluorimetric techniques of interest to clinical and pharmaceutical analyses. Thus, the performance of total fluorescence spectrometry in multicomponent and complex analyses has been assessed. The overall fluorescence of human serum and urine can be used as a diagnostic tool in clinical chemistry, particularly in view of its selectivity towards even quite small changes in the location of the peaks and their relative intensities. This is the foundation of pattern recognition methods for detection of pathological deviations from normal status. This technique is also suitable for rapid screening of a variety of drugs since the samples require virtually no treatment. 

Another example of dietary excess is the storage of surplus dietary energy as fat when there is chronic overeating. Normally, fattening is a natural activity of the body. However, if the deposition of fat results in marked obesity, there may be some pathological deviations from normal metabolism. For example, some obese persons have a diabeticlike underutilization of carbohydrates, fats, and proteins. They seem to secrete normal amounts of insulin, but the effects of the hormone appear to be hampered. Eventually, the pathology of diabetes may develop. 

Allergenic effect. Tests of PU elastomer extractions on rabbits [38] have not revealed any pathological deviations. Skin irritation effects on rats (hyperemia, hypostasis, dry skin, peeling, formation of ulcers) were not found. 

Duchateau, N., Craene, M.D., PieUa, G., Frangi, A.R Constrained manifold learning for the characterization of pathological deviations from normality. Medical Image Analysis 16, 1532-1549(2012)... 

Sufficient numbers of control animals should be employed. The use of such controls allows a determination of normal values for features monitored ki the study and background kicidence of pathology ki the population studied detection of the onset of adverse conditions, eg, infection, which are unrelated to, and detrimental to, the conduct of the study and deviation of monitored features between controls and exposed animals, which may kidicate a treatmentrelated effect. 

A significant contribution of rheo-NMR has been to show that the uniform shear-rate assumption may be violated in the case of certain classes of fluids in which pathological flow properties are exhibited. Figure 2.8.10 shows shear-rate maps [26] obtained for the wormlike surfactant system, cetylpyridinium chloride-sodium salicylate in water. While the velocity gradients show no deviation from uniformity at very low shear rates, above a certain critical value yc a dramatic variation in the rate-of-strain across the 7° cone gap is found. In particular a very high shear-rate band is found to exist at the mid-gap. 

Redox-inactive cations attract a particular interest for analytical chemists because of their importance in environmental control, industry, and medicine. For instance, in clinical diagnostics, tests for blood electrolytes (Na+, K+) are routine, because deviation of cation content from their normal values indicates a number of pathologies. 

The status of the study of variation and inheritance of structure in the central nervous system may be summarized as follows. The brain is extremely variable in every character that has been subjected to measurement. Its diversities of structure within the species are of the same general character as are the differences between related species or even between orders of animals. Some of the structural variations have been shown to correlate with functional disturbances. From what is known of the variations in other systems, it may be concluded that the variants which produce pathological symptoms are not discontinuous characters but are the extremes of a normal distribution. Lesser deviations in the same direction, resulting in behavior which is not classed as pathological, are to be expected. 

In autoimmunity models, similar interactions occur. Thus, mice exposed to S. mansoni ova are protected from two different autoimmune diseases, type 1 diabetes [71] and experimental allergic encephalomyelitis [72, 73]. In these instances, a Th2 immune deviation might equally explain the amelioration of Thl pathology, and experimental testing of this possibility remains to be undertaken. 

TNO has stated that the size, quality, completeness, and consistency of the database should be considered (Hakkert et al. 1996). Major aspects for the evaluation of the quality of the data supporting the NOAEL are (1) deviations from official guidelines, which are not properly substantiated, (2) number of animals used, (3) number of dose levels tested, and (4) adequacy of hematological, biochemical, and pathological examinations. Indications for doubts on the confidence in the database are (1) the absence of certain types of smdies, (2) conflicting results between studies, and (3) doubts on the reliability of the route-to-route extrapolation. However, consistency of results from different studies, consistency of animal and human data, and rehable mechanistic data are indicative for a high-confidence database. The default assessment factor for confidence of the database is 1. 

The (Cu,Zn)-SOD levels in erythrocytes of normal human subjects are fairly constant 461 46 (standard deviation) gg/g hemoglobin. Results are also reported for several pathological conditions Small differences were e.g. observed in erythrocytes with on the average a 19 % decrease in patients with Duchenne muscular dystrophy and a 20% increase in black alcoholics in contrast with white alcoholics Sickled erythrocytes showed significantly higher levels of (Cu,Zn)-SOD 170 % on the average of those of normal erythrocytes Tumor cells as a rule seem to have lower or zero levels of (Mn)-SOD... 

---