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Biomedical subjects

C Y Pak

Publications and source records attributed to C Y Pak.

At least 271 records · Page 15Linked to original sources

Enhancement of renal excretion of uric acid during long-term thiazide therapy.

The effect of thiazide (hydrochlorothiazide 100 mg per day orally in two divided doses for up to 3 years) on uric acid metabolism was examined in 21 patients with renal stones suffering from renal hypercalciuria or absorptive hypercalciuria. Serum concentration of uric acid increased during thiazide therapy in every patient. In 12 of 21 patients, there was a transient or persistent rise in urinary uric acid of more than 50 mg per day during treatment. The mean urinary uric acid produced by thiazide was positively correlated with the change in the renal clearance of uric acid. Thus, an increase in urinary uric acid was often associated with a rise in uric acid clearance. The results suggest that thiazide may either increase the production of uric acid or decrease the extrarenal disposal of uric acid, in some patients.

Administration, Oral↗

Metabolic effects of diphosphonate in primary hyperparathyroidism.

Six patients with primary hyperparathyroidism (PHPT) and one with squamous cell carcinoma of the esophagus with parathyroid hormone excess received disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at a daily dose of 20 mg/kg orally. During treatment, the decrease in urinary calcium, total urinary hydroxyproline, and fasting urinary calcium suggested an inhibition of bone resorption. Serum calcium intestinal absorption of calcium and urinary cyclic adenosine monophosphate (cAMP) did not change significantly. This preliminary study indicates a possible role of diphosphonates in the management of inoperable cases of primary hyperparathyroidism or pseudohyperparathyroidism.

Adult↗

Effect of hydrochlorothiazide therapy on the crystallization of calcium oxalate in urine.

The effect of hydrochlorothiazide on the formation of renal stones was evaluated by quantitative assessment of the propensity of urine to undergo crystallization of calcium oxalate. In seven patients with calcium urolithiasis (three with absorptive hypercalciuria, one with renal hypercalciuria, and three with normocalciuric nephrolithiasis), the urinary activity product ratio and formation product ratio of calcium oxalate were measured both on and off therapy with hydrochlorothiazide (50 mg orally twice a day). The activity product ratio (state of saturation with respect to calcium oxalate) decreased in the majority of cases, primarily as a result of the fall in urinary calcium. The formation product ratio (limit of metastability) increased in all cases; the cause of the increase was not readily apparent. Both changes reduced the propensity of urine to undergo crystallization of calcium oxalate, and therefore may account for the clinical improvement reported during thiazide therapy in nephrolithiasis.

Adult↗

Diagnosis of hyperparathyroidism.

States of hypersecretion of PTH may occur primarily, or in response to other physiologic abnormalities. Primary hyperparathyroidism must be considered in the differential diagnosis of hypercalcemia, nephrolithiasis, metabolic bone disease, and pancreatitis and peptic-ulcer disease. The clinical manifestations of this disease have become more subtle with improved detection. The serum calcium level is almost always elevated, and when it it accompanied by relatively high serum PTH levels or increased urinary cAMP excretion, the diagnosis is usually secure. Findings of hypophosphatemia, decreased renal tubular reabsorption of phosphorus, hypercalciuria, and characteristic roentgenographic changes support the diagnosis of hyperparathyroidism, but are not prerequisites for that diagnosis. Most cases will come to operation, and experienced intraoperative assessment is necessary for the correct distinction between multiglandular disease and that involving only a single gland. We expect that a clearer understanding of the histopathologic features of these diseases, and improvement in the methods for measurement of PTH will be the main areas of advancement in the diagnosis of hyperparathyroidism in the next few years.

Bone Diseases↗

Mechanism for calcium urolithiasis among patients with hyperuricosuria: supersaturation of urine with respect to monosodium urate.

Since monosodium urate (NaU) may play an important etiologic role in the formation of renal stones containing Ca in patients with hyperuricosuria, the current studies were undertaken to define some of the physiocochemical factors which determine the formation of NaU. In solutions containing Na, uric acid was rapidly transformed to NaU at pH greater than 6. The results indicated that NaU, and not uric acid, was the stable phase above this pH. A reliable and simple method for the calculation of the state of saturation of urine with respect to NaU was developed from the ratio of concentration products of Na and total dissolved urate (Upi) in the ambient fluid before and after incubation of urine with synthetic NaU. The concentration product ratio closely approximated the ratio of activity products of Na+ and acid urate ion. In contrast, the relative saturation ratio, or the ratio of activity product of original sample and the thermodynamic solubility product of NaU, often differed from the activity product ratio in the individual urine samples. With the concentration product rate, it was found in 45 urine samples that a critical determinant for the supersaturated state with respect to NaU was the high concentration of UT. At UT greater than 300 mg/liter, urine samples were invariably supersaturated with respect to NaU. These results suggest that the nidus of NaU could potentially form in the urine of patients with hyperuricosuria and Ca stones.

Calcium↗

The role of 1 alpha, 25-dihydroxyvitamin D in the mediation of intestinal hyperabsorption of calcium in primary hyperparathyroidism and absorptive hypercalciuria.

The cuase for the intestinal hyperabsorptionof calcium (Ca) in various forms of hypercalciurias was explored by a careful measurement of plasma 1 alpha, 25-dihydroxycholecalciferol [1 alpha, 25-(OH)I D] and by an assessment of intestinal Ca absorption and of parathyroid function. In 18 cases of primary hyperparathyroidism (PHPT), the mean plasma concentration of 1 alpha, 25-(OH)2D was significantly increased (4.9 +/- 2.2 SD ng/dl vs. 3.4 +/- 0.9 ng/dl for the control group), and was significantly correlated with fractional Ca absorption (alpha) (r = 0.80, P less than 0.001). Plasma 1 alpha, 25-(OH)2D was also correlated with urinary Ca (P less than 0.05), but not with serum Ca or phosphorus (P), P clearance, urinary cyclic AMP, or serum immunoreactive parathyroid hormone. In 21 cases of absorptive hypercalciuria (AH), plasma 1 alpha, 25-(OH)2D was elevated in one-third of cases, and the mean value of 4.5 +/- 1.1 ng/dl was significantly higher than that of the control group (P less than 0.01). Since relative hypoparathyroidism may be present, the normal absolute value of plasma 1 alpha, 25-(OH)2D, found in two-thirds of cases of AH, may be considered to be inappropriately high. Moreover, in the majority of cases of AH, the data points relating plasma 1 alpha, 25-(OH)2D and alpha fell within 95% confidence limits of values found in non-AH groups (including PHPT). The results suggest that the intestinal hyperabsorption of Ca in PHPT aw AH may be vitamin D dependent. However, the disturbance in vitamin D metabolism may not be the sole cause for the high Ca absorption in AH, since in some patients with AH, the intestinal Ca absorption appears to be inapp

Adult↗

Estimation of the state of saturation of brushite and calcium oxalate in urine: a comparison of three methods.

The estimation of the degree of saturation of brushite and of calcium oxalate in urine of patients with disorders of calcium metabolism has been proved to be an effective tool in evaluating the patient's propensity to form renal stones. The methods used in three different laboratories have been compared and evaluated in 27 urine samples. Relative saturation ratio (ratio of activity product and thermodynamic solubility product of brushite) and activity product ratio (ratio of activity product of original sample and that obtained after incubation of sample with synthetic brushite) were determined. Similar studies were performed for calcium oxalate. The values for relative saturation ratio of brushite or calcium oxalate differed widely among the three techniques. However, nearly identical values for activity product ratio of brushite were obtained. The activity product ratios of calcium oxalate, obtained by different techniques, closely approximated each other except in sampels containing excessive amounts of calcium (greater than 5 mM) or oxalate (greater than 5 mM). The values for the relative saturation ratios for both brushite and calcium oxalate were usually higher than the corresponding values for activity product ratio. The results indicate that the use of activity product ratio provides a more simple and reliable estimate of the urinary state of saturation than does the relative saturation ratio.

Ammonia↗

Nucleation and growth of brushite and calcium oxalate in urine of stone-formers.

The physicochemical factors involved in the formation of calcium-containing renal stones have been elucidated previously and some of the techniques for their quantitation are currently available. Accordingly, urinary activity product ratio (state of saturation), formation product ratio (limit of metastability), and crystal growth of brushite and calcium oxalate in 24-hr urine samples were compared between a control group without stones and stone-forming groups composed of patients with absorptive hypercalciuria, normocalciuric nephrolithiasis, and primary hyperparathyroidism. The activity product ratios of brushite and calcium oxalate were significantly elevated in stone-forming groups, largely because of the high renal excretion of calcium. The formation product ratios were reduced in most stone-forming groups, and the crystal growth was increased in the group with primary hyperparathyroidism. Thus, the physicochemical environment of urine in stone-forming groups was favorable to the nucleation of the nidi of brushite and calcium oxalate; in primary hyperparathyroidism, it may be conducive to the subsequent growth of nidi as well.

Adult↗

Jejunal and ileal absorption in patients with chronic renal disease. Effect of 1alpha-hydroxycholecalciferol.

Calcium absorption in 30-cm segments of small intestine was measured by constant perfusion of test solutions containing different concentrations of calcium gluconate. In both the jejunum and ileum, calcium absorption rates increased progressively as luminal calcium concentration was increased stepwise between 1 and 20 mM. Although calcium transport was not saturable within these limits, unidirectional flux ratios of calcium (47Ca) suggest that calcium absorption is active in both the jejunum and ileum. Calcium absorption in patients with chronic renal disease was markedly depressed in both regions of the small intestine. This was due to decreased flux out of the lumen; flux in the reverse direction was normal. Flux ratios in the renal disease patients showed no evidence for active calcium transport. Treatment of these patients for 1 wk within 2 mug/day of 1alpha-hydroxycholecalciferol [1alpha-(OH)-D3] restored net calcium absorption and unidirectional calcium flux out of the lumen to normal values in the jejunum; in the ileum, 1alpha-(OH)-D3 increased calcium absorption 60-83% of normal at the various luminal calcium concentrations. 1alpha(OH)-D3 had no effect on unidirectional calcium flux into the lumen or on xylose and electrolyte absorption in either area of the small intestine.

Biological Transport↗

Magnesium absorption in the human small intestine. Results in normal subjects, patients with chronic renal disease, and patients with absorptive hypercalciuria.

Magnesium absorption was studied in the normal human jejunum and ileum by in vivo intestinal perfusion, using test solutions containing from 0 to 20 mM Mg (as MgCl2). As luminal Mg concentration was increased, the rate of absorption in the jejunum rose progressively with a tendency towards saturation at the higher concentrations. The kinetics and rates of Mg absorption in the ileum were comparable to those in the jejunum, with the exception that at higher luminal concentrations the ileal absorptive process was fully saturated. Using test solutions containing various combinations of Ca and Mg, we found that Ca had little or no influence on Mg absorption, even through Mg depressed Ca absorption to a modest extent. Patients with end-stage renal disease, who had a reduced rate of Ca absorption (presumably due to deficiency of 1,25-dihydroxycholecalciferol) were found to have a severe depression of Mg absorption. On the other hand, patients with absorptive hypercalciuria and nephrolithiasis, who had an increased rate of Ca absorption, were found to absorb Mg normally. These results suggest that Mg absorption in the human is mediated by a transport process different from that which facilitates Ca absorption, and that normal Mg absorption may be dependent on vitamin D. Our results do not establish whether or not the normal intestine can absorb Mg against an electrochemical gradient.

Adult↗

Metabolic effects of parathyroidectomy in asymptomatic primary hyperparathyroidism.

Effects of parathyroidectomy on parathyroid function and calcium (Ca) metabolism were carefully evaluated in 6 patients with primary hyperparathyroidism without symptoms normally attributed to the disease and in 7 with bone disease or nephrolithiasis. Before parathyroidectomy, both groups of patients demonstrated evidence of the sequelae of parathyroid hormone (PTH) excess, since they presented one or more of the following features: low bone density by 125I-photon absorption, hypercalciuria (urinary Ca greater than 200 mg/day on an intake of 400 mg/day), negative Ca balance (absorbed Ca less than urinary Ca), elevated fasting urinary Ca greater than 0.2 mg/mg creatinine for a night-time sample after a 6-hour fast), and decreased renal function (creatinine clearance of less than 65 ml/min). Following parathyroidectomy, most of these deleterious effects were reversed commensurate with the return of immunoreactive serum PTH, serum Ca, and urinary cyclic AMP toward normal. These quantitative non-invasive techniques may be useful for the initial evaluation and follow-up of patients with asymptomatic primary hyperparathyroidism.

Adult↗

Photon absorptiometric analysis of bone density in primary hyperparathyroidism.

The density of bone in the distal third of the radius was measured in 13 men and 17 women with primary hyperparathyroidism. The bone density was significantly reduced (as compared to age-matched controls) in 7 of 11 postmenopausal women. However, it was reduced in only 2 of 13 men and in 1 of 6 premenopausal women. Thus, most of the postmenopausal women with primary hyperparathyroidism had low bone density, whereas most men and premenopausal women with this condition had normal bone density. The results support the conclusion that oestrogen deficiency may contribute to the development of bone disease by sensitising bone to the action of parathyroid hormone.

Adult↗

A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias.

A test was developed to diagnose various forms of hypercalciuria. A two-hour urine sample after an overnight fast and a four-hour urine sample after 1 g of calcium by mouth were tested for calcium, cyclic AMP and creatinine. The 24 patients with absorptive hypercalciuria had normocalcemia and normal fasting urinary calcium (less than 0.11 mg per milligram of urinary creatnine). Urinary calcium was high (greater than or equal to 0.2 mg per milligram of creatinine) after a calcium load. Of the 28 patients with primary hyperparathyroidism (resorptive hypercalciuria), 25 had hypercalcemia and 21 had high fasting urinary calcium. Urinary cyclic AMP, elevated in 30 per cent of fasting patients, was high (greater than 4.60 mu moles per gram of creatinine) in 82 per cent of cases after calcium load. Six patients with renal hypercalciuria had normocalcemia, high fasting urinary calcium, and high (greater than 6.86 mu moles per gram of creatinine) or high-normal fasting urinary cyclic AMP was normal. This simple test should facilitate the differentiation of various causes of hypercalciuria.

Bone Resorption↗

Effect of sodium cellulose phosphate therapy on crystallization of calcium oxalate in urine.

Effects of oral sodium cellulose phosphate therapy (5 g three times a day with meals for 4 days) on renal excretion of oxalate and on the crystallization of calcium oxalate in urine were examined in six patients with absorptive hypercalciuria on a constant metabolic dietary regimen. During treatment, urinary oxalate increased by 9-50 mg/day. However, urinary calcium decreased by 138-225 mg/day (50%-70%). Thus, the state of saturation of urine with respect to calcium oxalate decreased or did not change significantly. There was no consistent or significant change in the formation product ratio (limit of metastability) or in the crystal growth of calcium oxalate in urine.

Administration, Oral↗