Clinical significance

In conclusion for current discussion of multiple comparisons (discussions wiU resume in Chap. 5), it is not appropriate statistical practice to conduct many tests, find one statistically significant result, and present this lone result as a noteworthy finding. It is particularly not appropriate to present this result in the spirit that this is something that was anticipated before the study was conducted (i.e., that this was identified a priori as a comparison of interest). If a situation occurs in which one of many tests is significant, and it is believed that the result is biologically plausible and worthy of further investigation, a subsequent trial needs to be conducted, and this comparison needs to be identified in the study protocol as the primary comparison of interest. 

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Edwards, M. J. (1986). Hyperthermia as a teratogen A review of experimental. studies. and their clinical significance. Teratog. Carcinog. Mutag. 6, 56.3-S82. 

There is only one clinically significant penicillin at present that does not have an amide side chain. Mecill inam... 

R. R. Shah, J. M. Midgley, S. K. Branch, Stereochemical origin of some clinically significant dmg safety concerns lessons for future drug development. Adverse Drug React. Toxicol. Rev. 1998, 17, 145-190. 

Kopin IJ (1985) Catecholamine metabolism basic aspects and clinical significance. Pharmacol Rev 37(4) 333-364... 

Overproduction of the chromosomal genes for the dihydrofolate reductase (DHFR) and the dihydroptero-ate synthase (DHPS) leads to a decreased susceptibility to trimethoprim and sulfamethoxazol, respectively. This is thought to be the effect of titrating out the antibiotics. However, clinically significant resistance is always associated with amino acid changes within the target enzymes leading to a decreased affinity of the antibiotics. 

The human PR exists as two functionally distinct isoforms PRA and PRB transcribed from two promoters from a single gene. PRA lacks the N-terminal 164 aa and is a 769 aa protein. PRB functions as a transcriptional activator in most cell and promoter contexts. In contrast, PRA is transcriptionally inactive and functions as a strong ligand-dependent transdominant repressor of SHR transcriptional activity. Different cofactor interactions were demonstrated for PRA and PRB, probably due to an inhibitory domain within the first 140 aa of PRA, which is masked in PRB. Both PR isoforms however, repress estradiol-induced ER activity when liganded. Several other mRNA isoforms are present in PR-positive tissues such as breast cancer with unknown clinical significance. 

Multiple drug interactions may occur with the glucocorticoids. Table 50-2 identifies select clinically significant interactions. 

The Vaccine Adverse Event Reporting System (VAERS) is a national vaccine safety surveillance program co-sponsored by the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). VAERS collects and analyzes information from reports of adverse reactions after immunization. Anyone can report to VAERS, and reports are sent in by vaccine manufacturers, health care providers, and vaccine recipients and their parents or guardians. An example of the VAERS and instructions for completing the form are found in Appendix F. Any clinically significant adverse event that occurs after the administration of any vaccine should be reported. Individuals are encouraged to provide the information on the form even if the individual is uncertain if the event was related to the... 

The pretreatment of MH-susceptible patients with oral or intravenous dantrolene prior to surgery in order to avoid a crisis is controversial. Most physicians do not recommend prophylactic pretreatment except in patients who have had a previously documented episode. However, if pretreatment is desired, it is recommended that therapy be begun with intravenous dantrolene in a dose of 2 mg/Kg just prior to induction of anesthesia. This prevents the uncertainty of predictive blood values associated with the use of the oral route. The adverse effects of intravenous dantrolene prophylaxis include phlebitis and tissue necrosis. Patients who receive prophylactic treatment with oral dantrolene often complain of incapacitation, gastrointestinal irritation, prolonged drowsiness, and clinically significant respiratory muscle weakness. 

ADH also has clinical significance in the metabolism of methanol and ethylene glycol, two drugs with toxic metabolites. Methanol is oxidized by ADH to formaldehyde, which damages the retina and can cause blindness. Ethylene glycol is metabohzed by ADH to oxalic acid, which has renal tox-... 

B. The symptoms in Criterion A cause clinically significant distress or impairment in social, occupational, or other important areas of fimctioning. 

Walker, C.H. (1994b). Interactions between pesticides and esterases in humans. In M.I. Mackness and M. Clerc (Eds.) Esterases, Lipases, and Phospholipases from Structure to Clinical Significance. NATO ASI Series. Series A, Life Sciences. New York Plenum Press 91-98. 

Sugar Where Found Biochemical Importance Clinical Significance... 

The biosynthesis of purines and pyrimidines is stringently regulated and coordinated by feedback mechanisms that ensure their production in quantities and at times appropriate to varying physiologic demand. Genetic diseases of purine metabolism include gout, Lesch-Nyhan syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase deficiency. By contrast, apart from the orotic acidurias, there are few clinically significant disorders of pyrimidine catabolism. 

OVERPRODUCTION OF PYRIMIDINE CATABOLITES IS ONLY RARELY ASSOCIATED WITH CLINICALLY SIGNIFICANT ABNORMALITIES... 

Langlois MR, Delanghe JR Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 1996 2 1589. 

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