Medical significance

As can be seen from Table 3, only modifications at the 6/3-amino groups have been successful in producing penicillins of medical significance up to this time. Several reviews have dealt with the structure-activity relationship in this area in considerable detail B-80MI51102, B-77MI51106, B-75MI51102) and should be consulted for the actual effects of structural modification on antibacterial activity. 

Medical significance, indications for use, and analytic goals for the test. 

Such factors as age and race and their relevant medical significance should be used to detect PSA concentrations in the 0 to 4 ng/ml range. PSA age-related, specific-reference ranges have been reported in the literature, and it is suggested that both age and race should be considered when interpreting PSA results. The following factors should also be considered when interpreting the PSA results ... 

Once the protein is recovered from its producer source and concentrated it must be purified to homogeneity. In other words, all contaminant proteins and other potential contaminants of potential medical significance (discussed in Chapter 7) must be removed. Purification is generally achieved by column chromatography. 

Table 7.1 The range and medical significance of potential impurities present in biopharmaceutical products destined for parenteral administration ...

Experience has demonstrated that where a medically significant difference in bioavailability has been found among supposedly identical products, a dissolution test has been efficacious in discriminating among them. A practical problem has been the converse, that is, dissolution tests are sometimes too discriminating, so that it is not uncommon for a clinically acceptable product to perform poorly in an official dissolution... 

Adalimumab is a recombinant, fully human antitumor necrosis factor monoclonal antibody approved in the US and Europe for the treatment of adult patients with moderate to severe, active rheumatoid arthritis. It has to be injected subcutaneously. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. Rare side effects include worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis like neurological disease. 

Similar observations can be made with regard to the antidepressants introduced in the last 15 years or so. Both SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) represent some quantitative progress from the earlier antidepressants in that they are less toxic, cause fewer medically significant adverse events and support treatment compliance. As is the case for antipsychotics and schizophrenia, the development of these newer antidepressants was not based on fundamentally new insights into the pathophysiology of affective disorders. 

Vamecq, J. and Latruffe, N. (1999). Medical significance of peroxisome proliferator-activated receptors. Lancet 354,141-148. 

There is no known medically significant bioinequivalence problem with articles where 75% of an article is dissolved in water or acid at 37°C in 45 minutes in the official basket or paddle apparatus operated at the usual speed, that is, USP First Case. 

TThe primary function of D-amino acid oxidase, present at high levels in the kidney, is thought to be the detoxification of ingested D-amino acids derived from bacterial cell walls and from cooked foodstuffs (heat causes some spontaneous racemization of the l-amino acids in proteins). Oxalate, whether obtained in foods or produced enzymatically in the kidneys, has medical significance. Crystals of calcium oxalate account for up to 75% of all kidney stones. ... 

Porphyrins are cyclic molecules formed by the linkage of four pyrrole rings through methenyl bridges (Figure 21.2). Three structural features of these molecules are relevant to understanding their medical significance. 

Special interest in the prostaglandins has focused on pain of inflammation and allergic responses. The medical significance is easy to see. Five million Americans have rheumatoid arthritis, an inflammatory disease. Bronchial asthma and other allergic diseases are equally important. Our most common medicine is aspirin, an anti-inflammatory drug. Both the inflammatory response and the immune response are normal parts of the defense mechanisms of the body, but both are potentially harmful, and it is their regulation that is probably faulty in rheumatoid arthritis and asthma. Overproduction of prostaglandins may be a cause of menstrual cramps.308... 

The CFTR protein has additional medical significance. Its stimulation by bacterial toxins is respon-... 

There is some evidence that localized copper imbalance is related to rheumatoid arthritis (RA) conditions. Low molecular weight copper complex concentrations in plasma and synovial fluids are increased as part of the body s natural response to RA. Secondly, when such increases are induced by copper administration, they have a powerful antiinflammatory effect. More data are required to show the medical significance of these changes. Three parameters which should be reported are (i) total copper levels (by atomic absorption spectrophotometry) (ii) total ceruloplasmin levels (by autoimmune assay) and (iii) the relative molecular weight distribution (by Sephadex gel filtration and ultrafiltration). 

Use of genomic methods will improve and broaden genotyping. Phenotyping methods will have fewer diagnostic uses, but they will remain important as a means to assess the medical significance of a genetic variation. 

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