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Biomedical subjects

C Y Pak

Publications and source records attributed to C Y Pak.

At least 37 records · Page 2Linked to original sources
PubMed1998

Physiological effects of slow release potassium phosphate for absorptive hypercalciuria: a randomized double-blind trial.

PURPOSE: We examined the physiological effects and tolerance of UroPhos-K, a slow release neutral form of potassium phosphate (155 mg. phosphate and 8 mEq. potassium per tablet) in patients with absorptive hypercalciuria. MATERIALS AND METHODS: A total of 31 patients with absorptive hypercalciuria were studied at baseline and after 3 months of treatment with 4 tablets twice daily of UroPhos-K or placebo (identical in appearance) in a prospective randomized, placebo controlled, double-blind trial during a 4-day inpatient study with a daily constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate. RESULTS: Treatment with UroPhos-K did not cause significant gastrointestinal side effects, increase fasting serum potassium or phosphorus, or reduce hemoglobin or creatinine clearance. It reduced urinary calcium excretion from 277 +/- 72 to 166 +/- 43 mg. per day (p < 0.001), associated with a reduction in serum 1,25-dihydroxyvitamin D concentration from 50 +/- 11 to 42 +/- 9 pg./ml. (p < 0.001). Indexes of intestinal calcium absorption and markers of bone turnover also decreased modestly. None of these changes was seen in the placebo group. CONCLUSIONS: In patients with absorptive hypercalciuria UroPhos-K seems to correct hypercalciuria by a combination of reduced intestinal absorption, bone resorption and improved renal calcium reabsorption. The drug is well tolerated compared to placebo.

Adult↗
PubMed1998

Effect of potassium-magnesium citrate on upper gastrointestinal mucosa.

BACKGROUND: Potassium supplements may cause mucosal damage of the gastrointestinal tract. AIM: To evaluate the effect of a new potassium supplement, potassium-magnesium citrate (K-Mag), on upper gastrointestinal mucosa and to compare it with an older potassium supplement, potassium citrate (Urocit-K). METHODS: A randomized and double-blind study was conducted utilizing 36 healthy adults. Subjects were randomized into three groups: K-Mag (70 mmol/day K, 35 mmol/day citrate and 17.6 mmol/day Mg); Urocit-K (70 mmol/day K and 23.4 mmol/day citrate), and placebo. All subjects took 5 tablets b.d. of the allocated drug and 2 mg t.d.s. of glycopyrrolate for 7 days. On day 8, stool was examined for occult blood, a symptom score was calculated and an oesophagogastroduo-denoscopy was performed. Mucosal lesions were scored at five anatomic sites. RESULTS: Demographic characteristics and symptom score were similar in the three groups (< 10% with more than mild symptoms). There were no significant differences in the endoscopic scores at any site examined nor in the total scores among the three groups. Erosion or ulcers were found in 18% of K-Mag, 23% of Urocit-K and 17% of the placebo group. CONCLUSION: Short-term use of K-Mag does not appear to induce lesions in the upper gastrointestinal mucosa and its oral tolerance is similar to Urocit-K or placebo.

Adult↗
PubMed1998

Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia.

BACKGROUND: Angiotensin II stimulates the proximal tubular Na/H antiporter and increases proximal tubular cell pH. Because intracellular pH may affect urinary citrate excretion and enzymes responsible for renal citrate metabolism, the present studies examined the effect of enalapril, an angiotensin converting enzyme inhibitor, on the activity of renal cortical ATP citrate lyase and urinary citrate excretion. METHODS: Enalapril was given to rats (15 mg/kg/day) for seven days and to humans (10 mg twice daily) for 10 days. Blood and 24-hour urine samples were obtained in both groups. Renal cortical tissue from rats was analyzed for enzyme activity. RESULTS: In rats, enalapril decreased urinary citrate excretion by 88%. The change in urinary citrate was not associated with a difference in plasma pH, bicarbonate nor potassium concentration. However, similar to metabolic acidosis and hypokalemia, enalapril caused a 42% increase in renal cortical ATP citrate lyase activity. When given to humans, enalapril significantly decreased urinary citrate excretion and urine citrate concentration by 12% and 16%, respectively, without affecting plasma pH or electrolytes. CONCLUSIONS: Enalapril decreases urinary citrate in rats and humans. This is due, at least in part, to increases in cytosolic citrate metabolism through ATP citrate lyase in rats similar to that seen with chronic metabolic acidosis and hypokalemia. The effects of enalapril on urinary citrate and renal cortical ATP citrate lyase occur independently of acidosis or hypokalemia but may be due to intracellular acidosis that is common to all three conditions.

Acidosis↗
PubMed1998

Sustained reduction in urinary calcium during long-term treatment with slow release neutral potassium phosphate in absorptive hypercalciuria.

PURPOSE: We tested whether UroPhos-K, a new slow release neutral form of potassium phosphate (155 mg. phosphate, 8 mEq. potassium per tablet) in a dose of 4 tablets twice daily would produce a sustained hypocalciuric response and maintain bone mass in patients with absorptive hypercalciuria, a major cause of nephrolithiasis characterized by excessive intestinal calcium absorption accompanied in some patients by excessive bone loss. MATERIALS AND METHODS: A total of 25 patients with absorptive hypercalciuria were studied in a 4-year, prospective, open trial with UroPhos-K at yearly intervals during a 4-day inpatient physiological study with a constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate daily. RESULTS: Treatment with UroPhos-K caused a sustained, marked reduction in urinary calcium (264 to 181 mg. daily). Fractional 47calcium absorption decreased modestly (74.0 to 64.6%) commensurate with a reduction in serum 1,25-dihydroxyvitamin D (42 to 34 pg./ml.). Intact parathyroid hormone increased within the normal range (30 to 42 pg./ml.). Bone mineral density was stable at the lumbar spine, femoral neck and distal third of the radius. CONCLUSIONS: UroPhos-K may provide a long-term alternative for hypercalciuric patients in whom thiazide therapy fails.

Adult↗
PubMed1998

Normal vitamin D receptor concentration and responsiveness to 1, 25-dihydroxyvitamin D3 in skin fibroblasts from patients with absorptive hypercalciuria.

To evaluate whether there is an increase in vitamin D receptor (VDR) concentration which could raise intestinal calcium absorption in absorptive hypercalciuric (AH) patients and promote hypercalciuria, we measured VDR concentration and VDR mRNA levels in skin fibroblasts from 16 patients with AH and 17 age-matched normal subjects before and following a 16-hour incubation in the presence of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. There were no significant differences in VDR concentration between normal subjects and AH patients in the basal state (30 +/- 11 vs. 30 +/- 15 ng/mg protein, respectively) or following 1,25(OH)2D3-mediated upregulation (43 +/- 18 vs. 42 +/- 16 ng/mg protein) as measured by immunoblot methodology. Analysis of VDR mRNA/beta-actin mRNA ratios demonstrated no significant differences between normal subjects and AH patients prior to (2.1 +/- 1.7 vs. 1.8 +/- 2.4) or following (2.7 +/- 2.8 vs. 1.9 +/- 1.8) 1,25(OH)2D3 exposure. As a measure of VDR bioactivity, we quantitated 1,25(OH)2D3-mediated induction of 25-hydroxyvitamin D3-24-hydroxylase. Again, no significant differences were observed between normal subjects and all patients (2.1 +/- 1.6 vs. 1.9 +/- 1.6 pmol/mg/30 min, respectively). These findings indicate that there is neither an increase in VDR concentration in skin fibroblasts, a recognized vitamin D responsive cell, nor increased sensitivity to upregulation of VDR numbers by 1, 25(OH)2D3 in patients with AH. This suggests an alternative cause of intestinal hyperabsorption of calcium in AH other than alteration of the VDR number.

Absorption↗
PubMed1998

The effect of varying molar ratios of potassium-magnesium citrate on thiazide-induced hypokalemia and magnesium loss.

This study was conducted to compare the value of an older formulation of potassium-magnesium citrate (K4MgCit2) with newer formulations (K3MgHCit2 and K5MgCit2Cl) with respect to the correction of thiazide-induced hypokalemia and magnesium loss, alkalinizing effect, and citraturic action. Sixty-two healthy volunteers first took hydrochlorothiazide 50 mg/day. After 3 weeks of thiazide treatment (or earlier if hypokalemia developed), they were randomized to take one of three drugs for 3 weeks while continuing thiazide: K4MgCit2 (49 mEq K, 25 mEq Mg, and 74 mEq citrate/day), K3MgHCit2 (49 mEq K, 33 mEq Mg, and 98 mEq citrate/day), and K5MgCit2Cl (49 mEq K, 20 mEq Mg, 10 mEq Cl and 59 mEq citrate/day). Outcome measures were changes in serum potassium and magnesium, and urinary potassium, magnesium, pH, and citrate. The three drugs were equally effective in correcting thiazide-induced hypokalemia. K3MgHCit2 and K4MgCit2 produced a small but significant increase in serum magnesium concentration, whereas K5MgCit2Cl did not. Although all three supplements significantly increased urinary pH and citrate, these effects were more marked with K3MgHCit2 and K4MgCit2 than with K5MgCit2. All three supplements were generally well tolerated, with the lowest side effect profile obtained with K4MgCit2. The new formulation of K3MgHCit2 exerts similar correction of thiazide-induced hypokalemia and magnesium loss, and enhancement of urinary pH and citrate, compared with the older K4MgCit2. However, it is less well tolerated. The new formulation of K5MgCit2Cl does not avert magnesium loss, and has less prominent alkalinizing and citraturic effects than the older preparation.

Adult↗
PubMed1998

Mutations in the genomic deoxyribonucleic acid for SLC3A1 in patients with cystinuria.

Cystinuria is an inherited transport disorder characterized by defective renal resorption of cystine and other dibasic amino acids. We have studied the occurrence of mutations in the SLC3A1 gene, which codes for a dibasic amino acid transporter-like protein, in 33 unrelated cystinurics. We found mutations in 34 of the 66 chromosomes studied. There were 14 different mutations in our study population, 8 of which had not been previously described. Of these new mutations, 4 were missense mutations: G1934C, C1259G, T1607G, and G1373A. The other 4 mutations consisted of a single base insertion mutation (2022 ins T), a single base deletion mutation (163 del C), a 23-base deletion mutation (del 782A-804A), and a complex mutation that consisted of a 36-base deletion (del C431-3 to T463) and a duplication insertion of 468 T to 474 A after nucleotide 474.

Adolescent↗
PubMed1998

The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects.

This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.

Adult↗
PubMed1997

The effect of intermittent slow-release sodium fluoride and continuous calcium citrate therapy on calcitropic hormones, biochemical markers of bone metabolism, and blood chemistry in postmenopausal osteoporosis.

A detailed examination of calcitropic hormones and biochemical markers of bone turnover, serum chemistry, and blood hematology was performed in 75 postmenopausal women allocated to two groups: placebo plus calcium citrate (400 mg Ca B.I.D.) (n = 36) or intermittent slow-release sodium fluoride (SRNaF, 25 mg B.I.D.) plus calcium citrate (n = 39). After 2 years of therapy, a significant reduction in serum immunoreactive parathyroid hormone (PTH) was seen for both groups (43 +/- 18 SD-30 +/- 11 ng/liter, in placebo and 46 +/- 24-36 +/- 10, in SRNaF P < 0.0001 for both groups). Serum 1, 25(OH)2D significantly fell in placebo-treated patients (91 +/- 31-75 +/- 34 pmol/liter, P = 0.001) but did not change for SRNaF-treated patients. This difference in response between placebo and SRNaF-treated groups was significant, P = 0.005. Urinary hydroxyproline significantly declined during treatment in both groups (130 +/- 61-76 +/- 38 micromol/day, for placebo and 138 +/- 84-84 +/- 38 for SRNaF, P = 0.001). Similar decreases in urinary N-telopeptide of type I collagen were also observed for both groups (305 +/- 192-252 +/- 197 nmoles BCE/day for placebo and 356 +/- 230-220 +/- 197, P = 0.0001 for SRNaF). Serum carboxyterminal propeptide of type I collagen (PICP) declined significantly in both the placebo and SRNaF groups (118 +/- 38-101 +/- 36 microg/liter, and 116 +/- 47-105 +/- 39, P = 0.0027). Serum osteocalcin did not change significantly for either group, but bone-specific alkaline phosphatase (BS-ALPase), another marker of bone formation, demonstrated a significant fall in the placebo group at 2 years of therapy (16.2 +/- 6.7 U/liter-12.1 +/- 3.5, P = 0.009) and a small increase in the SRNaF-treated patients (13.0 +/- 4.1-15.0 +/- 4.5). The observed difference in response of BS-ALPase between the placebo and treated groups was significant (P = 0.007). There were no significant changes within or between treatment groups for blood hematology or serum chemistries. Mean values for all parameters remained within established normal ranges. These findings suggest that administration of calcium citrate inhibited PTH secretion and thereby reduced bone resorption in both groups, indicated by a decline in serum PTH, urinary hydroxyproline, and N-telopeptide. A low turnover state of bone may have been produced in the placebo group taking calcium citrate alone, since serum PICP, BS-ALPase, and 1,25(OH)2D also decreased. The addition of SRNaF prevented serum 1, 25(OH)2D from falling by an unknown mechanism. However, its anabolic action on the skeleton was best reflected by changes in BS-ALPase. Moreover, SRNaF appeared to exert no deleterious effects on blood chemistries or hematology during 2 years of administration.

Alkaline Phosphatase↗
PubMed1997

Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis.

PURPOSE: We examined the efficacy of potassium-magnesium citrate in preventing recurrent calcium oxalate kidney calculi. MATERIALS AND METHODS: We conducted a prospective double-blind study of 64 patients who were randomly assigned to receive placebo or potassium-magnesium citrate (42 mEq. potassium, 21 mEq. magnesium, and 63 mEq. citrate) daily for up to 3 years. RESULTS. New calculi formed in 63.6% of subjects receiving placebo and in 12.9% of subjects receiving potassium-magnesium citrate. When compared with placebo, the relative risk of treatment failure for potassium-magnesium citrate was 0.16 (95% confidence interval 0.05 to 0.46). Potassium-magnesium citrate had a statistically significant effect (relative risk 0.10, 95% confidence interval 0.03 to 0.36) even after adjustment for possible confounders, including age, pretreatment calculous event rate and urinary biochemical abnormalities. CONCLUSIONS: Potassium-magnesium citrate effectively prevents recurrent calcium oxalate stones, and this treatment given for up to 3 years reduces risk of recurrence by 85%.

Adult↗
PubMed1997

Renal stone risk assessment during Space Shuttle flights.

PURPOSE: The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. MATERIALS AND METHODS: 24-hr. urine samples were collected prior to, during space flight, and following landing. Urinary and dietary factors associated with renal stone formation were analyzed and the relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. RESULTS: Urinary composition changed during flight to favor the crystallization of calcium-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. CONCLUSIONS: This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. Dietary and pharmacologic therapies need to be assessed to minimize the potential for renal stone formation in astronauts during/after space flight.

Adult↗
PubMed1997

Ethnic and geographic diversity of stone disease.

OBJECTIVES: To ascertain diversity or similarity in stone prevention and problems among different countries around the world. METHODS: Urolithiasis research groups from 10 countries completed a questionnaire. RESULTS: Cost of extracorporeal shock wave lithotripsy (ESWL) was considerably greater than that of drugs in four countries, and equivalent in remaining countries. Stone composition was similar among different countries. Certain urinary risk factors were associated with particular countries, probably from dietary indiscretions. ESWL was used in the majority of patients and open surgery in a minority of patients, except in one country. Medical diagnostic evaluation was used in the majority of patients except in one country. Drug treatment was nonselective, and provided to a minority of recurrent stone-formers. CONCLUSIONS: There is considerable similarity in stone presentations and problems throughout the world. The diversity is likely to be due to nutritional-environmental and socio-political-economic factors.

Cost-Benefit Analysis↗
PubMed1997

Medical therapy, calcium oxalate urolithiasis.

The development of diagnostic protocols that identify specific risk factors for calcium oxalate nephrolithiasis has led to the formulation of directed medical regimens that are aimed at correcting the underlying metabolic disturbances. Initiation of these treatment programs has reduced markedly the rate of stone formation in the majority of patients who form stones. This article discusses the rationale that underlies the choice of medical therapy for the various pathophysiologic causes of calcium oxalate nephrolithiasis and the appropriate use of available medications.

Calcium↗
PubMed1997

Southwestern Internal Medicine Conference: medical management of nephrolithiasis--a new, simplified approach for general practice.

Considerable progress has been made regarding pathophysiology, diagnosis, and medical prevention of recurrent renal stone formation. The medical approach is not applied widely because of the availability of extracorporeal shockwave lithotripsy and the complexity of medical diagnostic and treatment modalities. In this review, a simplified program for the medical management of stones is described. From analysis of stone risk factors in 24-hour urine specimens, uncomplicated calcium stone disease is separated from other stone diseases. The uncomplicated calcium stone disease, comprising the illness in the majority of patients with recurrent renal calculi, is characterized by normocalcemia, normouricemia, calcium stones, and the absence of urinary tract infection, bowel disease, or marked hyperoxaluria. Uncomplicated calcium stone disease is separated into a hypercalciuric group and a normocalciuric group. In the simplified treatment program, the hypercalciuric group would be offered thiazide plus potassium citrate, whereas the normocalciuric group would receive potassium citrate alone.

Benzothiadiazines↗
PubMed1997

Connectivity in human cancellous bone by three-dimensional magnetic resonance imaging.

Bone architecture affects strength and resistance to fracture. Trabecular connectivity is now recognized as an important measure of bone quality, and could be useful as an indicator of the osteoporotic condition, as well as a tool for measuring the effectiveness of therapies. We have applied three-dimensional magnetic resonance imaging microscopy to human cancellous bone biopsies, and report the results of connectivity measurements. Sample heterogeneity was examined on the basis of connectivity density for subvolumes. The choice of examination volume had a significant effect on connectivity density measurements, but sample volumes greater than 100 mm3 were found to give stable results. Connectivity density was strongly correlated with nodal density, and two-dimensional estimates of connectivity, but not bone volume fraction. Repeat measurement at constant resolution (69 x 138 x 109 microns, signal-to-noise ratio of about 35) showed reproducibility of about 5% for connectivity density. Our most recent results have significantly enhanced resolution (69 x 69 x 43 microns); bone fraction remained constant, but apparent connectivity density is greater.

Algorithms↗
PubMed1997

Reflection ultrasound velocities and histomorphometric and connectivity analyses: correlations and effect of slow-release sodium fluoride.

To better understand how structural and functional bone properties contribute to the changes in bone biomechanical properties revealed by ultrasound critical angle reflectometry (UCR) analysis, we measured both UCR velocities and histomorphometric properties in bone biopsy specimens from 33 osteoporotic patients before and following intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate administration. Mean skeletal fluoride exposure was 17 months, and mean skeletal fluoride content was 0.203 +/- 0.088 SD% bone ash. Intermittent SRNaF and continuous calcium citrate promoted significant increases in trabecular thickness (122 +/- 18 SD microm to 131 +/- 20, p = 0.020), mineral apposition rate (0.79 +/- 0.26 to 1.05 +/- 0.40 microm/day, p = 0.014), and a significant decline in eroded surface (3.9 +/- 1.6 to 2.8 +/- 1.4%, p = 0.002). There were also significant increases in node number (0.193 +/- 0.100 to 0.368 +/- 0.245, p < 0.01) and node-to-node strut length (0.076 +/- 0.087 to 0.191 +/- 0.173, p < 0.01) relative to total cancellous area. Cortical UCR velocity did not change but cancellous velocity significantly increased by 97 m/s following therapy (p = 0.0005). When compared against the significant changes in bone histomorphometry and connectivity, the sum of both cancellous and cortical ultrasound velocities was significantly correlated with node number/area (R2 = 0.305, p < 0.0001) and node-to-node strut length/area (R2 = 0.372, p < 0.0001) and to a lesser extent with mineral apposition rate (R2 = 0.106, p = 0.032). Multiple regression analysis demonstrated that 40% of the variance in the sum of the UCR velocities can be accounted for by the variability in these histomorphometric and connectivity parameters. There were no significant correlations between the sum of cortical and cancellous ultrasound velocities and cancellous bone volume (R2 = 0.014, p = 0533), trabecular thickness (R2 = 0.012, p = 0.47), or bone mineral density (R2 = 0.003, p = 0.80). These observations indicate that velocity measurements with the UCR methodology show an improvement in bone elasticity associated, in part, with an improvement in the rate of bone mineralization and an improvement in bone quality at the structural level as shown by microarchitecture.

Adult↗