Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bone adenylyl cyclase (AC) complex of iliac crest biopsies of normals, uremic patients and subjects with primary hyperparathyroidism (PrHPT) have been investigated. Bone resorption (RS) in uremic patients appears to be related partly to increased serum parathyroid hormone (s-PTH) levels and to netto PTH-stimulated AC (net PTH-AC) and partly to the uremic condition (as estimated by s-Creatinine) per se. Serum PTH is able to completely desensitize the PTH dependent bone AC in normals in vivo, but only partially in uremic patients. In patients with PrHPT, the bone AC appears to be inert to homologous desensitization. Positive aluminum staining is associated with blunted CT-responsive and low basal AC. In the combined group of normals and uremic patients, net PTH-AC is (as predicted from human in vitro data and the rat model) inversely related to serum 24,25-diOH-D3. Net PTH-AC, when corrected for s-24,25-diOH-D3 levels, correlated well with RS. The described action of 24,25-diOH-D3 presents a clearly defined rationale for the use of 24,25-diOH-D3 concurrently with 1,25-diOH-D3 to treat renal osteodystrophy: By administering 1,25-diOH-D3, s-Ca2+ and s-PTH will normalize and consequently net PTH-AC diminish. 24,25-diOH-D3 is then believed to further reduce net PTH-AC and RS. A concomitant alleviation of the uremic condition would eventually ensure the fastest possible restoration of bone structure and function.
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PMID:The effect of parathyroid hormone (PTH) and 24,25-dihydroxy-vitamin D3 on adenylyl cyclase of iliac crest biopsies: diagnostic and prognostic tool for evaluation and treatment of uremic patients. 349 56

Twenty-five normal subjects, 45 patients with idiopathic hypercalciuria, and 50 patients with primary hyperparathyroidism were studied with an oral calcium tolerance test and with measurements of 24-h calcium and total cAMP excretion on defined 400-mg and 1000-mg calcium diets. There was a strong positive correlation (r = 0.62; P less than 0.001) between the calciuric response to the tolerance test and the increase in calcium excretion on the 100-mg relative to the 400-mg calcium diet. The increase in daily calcium intake was associated with a significant (P less than 0.001) suppression in total cAMP excretion in each patient group. The suppression in cAMP excretion was sufficient to completely segregate patients with absorptive hypercalciuria from those with renal hypercalciuria on the 1000-mg calcium diet (ranges, 1.24-3.50 and 3.97-4.87 nmol/100 ml glomerular filtrate, respectively). In patients with primary hyperparathyroidism, results for total cAMP excretion were elevated in 48 (96%) patients on the restricted calcium diet but were within the normal range in 14 (28%) patients on the high-normal calcium diet. Net intestinal calcium absorption has a prominent influence on results for 24-h total cAMP excretion, which may be used to diagnostic advantage or seriously impair diagnostic accuracy, depending upon the patient population and the conditions of study.
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PMID:The influence of calcium intake and the status of intestinal calcium absorption on the diagnostic utility of measurements of 24-hour cyclic adenosine 3',5'-monophosphate excretion. 626 62

Iliac crest biopsies of normals, uremic patients and subjects with primary hyperparathyroidism (pHPT) were investigated. It appeared that serum 1,25- and 24,25-(OH)2-D3 correlated inversely with basal adenylate cyclase (AC) activity and relative PTH-stimulated AC, respectively. Net PTH-elicited AC (dPTH-AC) activation hence reflected individual vitamin D status. The combination variable serum PTH (s-PTH) x dPTH-AC x [H+] correlated well with resorption surface (RS) in both normals, patients with pHPT or subjects with uremia, while s-PTH, dPTH-AC activity or pH as single variables were only marginally related to RS. For all subjects analyzed, osteoid volume (OV) correlated positively with serum alkaline phosphatase but negatively with serum 1,25-(OH)2-D3. OV showed no correlation with dPTH-AC, while the relationship between OV and s-PTH was strong, suggesting that PTH stimulates osteoid deposition via some signalling pathway other than cAMP. In normals, OV was inversely proportional to s-PTH, due to homologous desensitization of this signalling system. Furthermore, s-PTH was negatively correlated with urine cAMP due to homologous desensitization of the effect of PTH on the kidney 25-(OH)-D3 1 alpha-hydroxylase. This phenomenon was absent in uremic patients. Evaluation of variables by artificial intelligence showed that the prototype uremic patient exhibited serum creatinine > 900 microM, RS > 0.12, pH between 7.15 and 7.34 and s-PTH x dPTH-AC x [H+] between 0.5 and 3.7 units with the distinguishability index 'very good' (< 5% overlap) towards normals. Average similarity of uremic patients with the prototype for normal subjects was only 22%. Cluster analysis of all the variables was conducted for comparison and yielded less clinically relevant information. Hence, emulation done by the expert system was superior and clearly indicates that present treatment modalities restore normal bone turnover only to a minor degree or not at all.
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PMID:PTH-stimulated adenylate cyclase activity and bone histomorphometry in iliac crest biopsies in the evaluation of uremic patients: a pilot study with the use of artificial intelligence. 816 16