Abnormalities, obscure

The pathogenic mechanisms responsible for the association of musculoskeletal abnormalities with hypercholesterolaemia remain obscure. However, it has been hypothesized that the deposition and modification of lipoprotein components within and around the joint of patients with hyperlipidaemia-associated arthropathy results in a pro-inflammatory response, giving rise to articular disorders (Prete et al., 1993). 

The fibroblasts do not convert cyanocobalamin or hydroxocobalamin to methylcobalamin or adenosyl-cobalamin, resulting in diminished activity of both N5-methyltetrahydrofolate homocysteine methyltransferase and methylmalonyl-CoA mutase. Supplementation with hydroxocobalamin rectifies the aberrant biochemistry. The precise nature of the underlying defect remains obscure. Diagnosis should be suspected in a child with homocystinuria, methylmalonic aciduria, megaloblastic anemia, hypomethioninemia and normal blood levels of folate and vitamin B12. A definitive diagnosis requires demonstration of these abnormalities in fibroblasts. Prenatal diagnosis is possible. 

We now know that there is nothing abnormal about the urine of manic patients. In all probability, lithium appears to calm guinea pigs only because it makes them sick. Nevertheless, his clinical results were sufficiently positive that Cade published the results in an obscure Australian journal in 1949. In 1954, a Danish psychiatrist confirmed Cade s findings and the use of lithium began to spread in Europe. It was not until the mid-1960s, however, that lithium was marketed commercially in the United States, but it was not used for the treatment of mania until 1970. 

Statistical tests should only be carefully (directly) applied as acceptance criteria due to the small number of data normally obtained. Sometimes, because of abnormally small variabilities in the analytical series, differences are identified as significant which are of no practical relevance. In addition, when comparing independent methods for the proof of accuracy, different specificities can be expected which add a systematic bias, thus increasing the risk of the aforementioned danger. The analyst must decide whether detected statistical differences are of practical relevance. On the other hand, a large variability can also obscure differences which are not acceptable. If validation software is used, it must be flexible enough to meet these precautions. ... 

Zinc supplementation to these patients led to complete clearance of skin lesions and restoration of normal bowel function, which had previously resisted various dietary and drug regimens. This original observation was quickly confirmed in other cases with equally good results. The underlying mechanism of the zinc deficiency in these patients is most likely attributable to malabsorption. The cause of poor absorption is obscure, but an abnormality of Paneth s cells may be involved. These observations should provide a great stimulus to all interested in zinc metabolism to look for manifestations of zinc deficiency in other disorders, either natural or induced, in both children and adults. 

In some cases the kinetic currents are small (sometimes 10% or even less) even at their maximum height when compared with waves of the equimolar solutions that are diffusion-controlled. This type of behaviour has been observed in particular in systems in which the waves of are obscured by the supporting electrolyte. However, not all kinetic currents are so small and whilst abnormally small currents may indicate kinetic currents, currents of the normal height do not allow us to exclude the role of chemical reactions. (Some catalytic currents are abnormally high.)... 

Familial dysautonomia, dopamine [i-liydroxylase deficiency, norepinephrine transporter deficiency, and congenital adrenal hyperplasia include dysautonomias or conditions associated with adrenal medullary dysfunction in which the specific genetic abnormalities have been identified. There are also other disorders involving mutations of genes coding for proteins involved in catecholamine synthesis and metabolism in which the clinical manifestations do not clearly involve the sympathoadrenal systems or may be so globally severe that abnormalities of autonomic or adrenal medullary function are obscured (Table 29-5). 

Figure VI-1 shows normal and some abnormal patterns of serum protein electrophoresis. The electrophoretic patterns obtained are not indicative of any one disease or class of disease. Furthermore, a characteristic pattern may be obscured or not found in a disease entity where normally such a pattern is expected. Serum electrophoretic patterns provide only a general impression of the disorder and require confirmation by other procedures. An alteration (depression or elevation) in a given fraction should be quantitated by more sensitive and specific methods.

In addition, the influence of recurrent respiratory tract infections during childhood or young adult life on the later development of chronic bronchitis remains obscure. Recurrent respiratory infections at a young age may predispose individuals to the development of chronic bronchitis however, it is unclear whether these recurrent respiratory tract infections are a result of unrecognized anatomic abnormalities of the airways or impaired pulmonary defense mecha-... 

Iodine-induced thyrotoxicosis in apparently normal thyroid glands has been reported in two patients after exposure to 2—10 mg iodine daily for 2—12 months before thyrotoxicosis was diagnosed. Although the pathogenesis of this kind of IIH remains obscure, the positive family history for thyroid disease in both patients may indicate a latent abnormality of their thyroid glands (Skare and Frey, 1980). Moreover, 10 further cases of iodine-induced thyrotoxicosis in apparently normal thyroid glands have been reported (Savoie et al, 1975). In contrast, a more-than-adequate or excessive iodine intake may lead to hypothyroidism and autoimmune thyroiditis, as shown in China in areas with more than adequate and excessive iodine consumption (Teng et al., 2006). 

Binding of (3-lactam antibiotics to PBP-1A and PBP-1 B (transpeptidase) of Escherichia coii leads to cell lysis to PBP-2 (transpeptidase) leads to oval cells deficient in rigidity and to inhibition of cell division to PBP-3 (transpeptidase) leads to abnormally long, filamentous shapes by failure to produce a septum and to PBP-4 through PBP-6 (carboxypeptidases) leads to no lethal effects. Approximately 8% of a dose of benzylpenicillin binds to PCP-1, 0.7% to PCP-2, 2% to PBP-3, 4% to PBP-4, 65% to PBP-5, and 21% to PBP-6. Thus, the majority of the penicillin dose bonds to PBPs for which the function remains obscure. Binding to PBP-1 is lethal. Other (3-lactam antibiotics display different binding patterns. Amoxicillin and the cephalosporins bind more avidly to PBP-1, methicillin and cefotaxime to PBP-2, and mezlocillin and cefuroxime to PBP-3. All these drugs are lethal to susceptible bacteria. 

Obviously the greatest interest now centers on stress situations. Under some conditions kno to deplete ascorbic acid in the adrenal cortex of animals there is also evidence of an increased catabolism of the vitamin in man. After bums and fractures (Andreae and Browne, 1946) and also in active rheumatoid arthritis (Hall d al., 1939) the level of reduced ascorbic acid in the plasma has been found to be low, requiring unusually large doses to raise it. Apparently the vitamin is used up with abnormal speed in these conditions, thou the mechanism involved is obscure. It is difficult to believe that it is all destroyed in the adrenal cortex under the influence of ACTH discharged from the anterior pituitary, because the amount in the cortex at any one moment is infinitesimal (Section III, 2) compared with the amount that may appear to be lost from the body. According to Sayers et al. (1946), ACTH does not deplete other organs of ascorbic acid, at least in the rat and guinea pig. Perhaps the vitamin is not really destroyed, but merely shifted over to the oxidized form (DHA). 

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