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Biomedical subjects

J R Klinenberg

Publications and source records attributed to J R Klinenberg.

105 records · Page 6Linked to original sources
PubMed1969

Current concepts of hyperuricemia and gout.

Recent studies have confirmed that gout is an inborn error of metabolism. It has now become evident that the hyperuricemia associated with gout might occur either due to overproduction of uric acid, underexcretion of uric acid or a combination of these processes. Furthermore, patients with excessive purine synthesis may have a specific enzyme defect resulting in altered feedback inhibition of purine synthesis. A neurological disease manifest by mental retardation, choreo-athetosis, aggressive behavior, lip-biting and self-mutilation and associated with decidedly increased purine biosynthesis serves as a prototype of this kind of disorder. Other defects in regulation of purine biosynthesis have been postulated but their existence not yet confirmed. It has been demonstrated that urate crystals which are deposited from hyperuricemic body fluids set up an acute inflammatory reaction by means of a variety of chemical mediators. Thus, acute gouty arthritis is now recognized as an example of "crystal induced" synovitis. The treatment of gout consists of (1) the control of acute gouty attacks, and (2) the maintenance of normal serum uric acid concentrations. This latter may be achieved either with uricosuric drugs or with xanthine oxidase inhibition. With these principles in mind, it is now possible to avoid many of the severe crippling effects of gout and to restore the vast majority of gouty patients to useful and productive lives.

Chemical Phenomena↗
PubMed1968

Suppression of glycine-15N incorporation into urinary uric acid by adenine-8-13C in normal and gouty subjects.

Adenine inhibited the de novo synthesis of purines in both normal and gouty man as shown by inhibition of the incorporation of glycine-(15)N into urinary uric acid without altering the incorporation of glycine-(15)N into urinary creatinine. The diminished purine synthesis did not result in a diminution in the 24 hr excretion of uric acid. This observation was explainable in part by the prompt conversion of adenine to uric acid. In addition to this direct conversion, adenine-8-(13)C provided a slow and prolonged contribution to urinary uric acid.A feedback inhibition of purine synthesis by nucleotides derived from adenine provides the best interpretation of these results.

Adenine Nucleotides↗
PubMedDate not supplied

Halofenate. Its selection and trial as a primary uricosuric agent.

In vitro binding studies on antiinflammatory and uricosuric acidic anions performed under "physiologic" conditions have demonstrated that these substances displace urate from its protein bond. The property of urate displacement appears to be a useful marker for potential uricosuric activity in vivo, and thereby a means to detect novel uricosuric drugs. One such drug, halofenate, was indeed a safe and effective uricosuric (comparable to probenecid) when used to treat hyperuricemia/gout over the long term; it did result in a modest and variable fall in serum lipid concentrations. However, used as a single fixed dose, halofenate did not produce a marked and consistent effect on the elevated serum triglyceride concentrations so commonly present in gouty patients.

Adult↗
PubMedDate not supplied

The use of endomyocardial biopsy in a serious cardiac abnormality associated with polymyositis: a case report.

Life-threatening cardiac abnormalities in polymyositis (PM) patients may result from myocardial inflammation, fibrosis, or another disease process. Few procedures have reliably identified the pathologic basis for these abnormalities. We report a patient with PM, severe congestive cardiomyopathy, and life-threatening ventricular arrhythmias in whom an endomyocardial biopsy was done. The histopathological findings of fibrosis without inflammation, which were confirmed at autopsy, facilitated the decision to treat the patient symptomatically without intensification of antiinflammatory therapy. Endomyocardial biopsy may be a useful technique to determine the exact nature of serious cardiac abnormalities in PM patients so that appropriate therapy may be given.

Adult↗