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C Y Pak

Publications and source records attributed to C Y Pak.

At least 19 recordsLinked to original sources
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↗
PubMed1996

Comparison of nonrandomized trials with slow-release sodium fluoride with a randomized placebo-controlled trial in postmenopausal osteoporosis.

The results of slow-release sodium fluoride (SR-NaF) treatment in two nonrandomized trials involving 65 patients with postmenopausal osteoporosis from the primary site and 121 patients from collaborative sites were compared with those obtained from 54 treated patients and 56 patients taking placebo from a randomized controlled trial. Spinal fracture data were analyzed separately in mild to moderate bone loss of lumbar spine (baseline L2-L4 bone density [BD] > or = 65% young normal) and in severe bone loss (BD < 65%). Since demographic and fracture data were similar among fluoride-treated patients from the three trials at each stratum of bone loss, their data were combined. In mild to moderate bone loss, SR-NaF treatment in the combined group virtually eliminated new spinal fractures with 96.6% of patients remaining fracture-free. The Fluoride group had a markedly lower individual vertebral fracture rate (0.025 vs. 0.188/patient year, p = 0.0001) and group vertebral fracture rate (0.029 vs. 0.175/patient year, relative risk [RR] 0.12, p = 0.0001) than the Placebo group. In severe bone loss, the combined treated group had a significantly lower new spinal fracture rate than the Placebo group, although the differences were not as marked (group vertebral fracture rate of 0.150 vs. 0.276/patient year, RR 0.54, p = 0.03). In the combined fluoride-treated group, the L2-L4 bone mass rose by 4-6%/year for 4 years, and the femoral neck BD increased by 1-2%/year during first 2 years. The radial shaft BD did not change. The Placebo group did not show a change in bone mass at any site. The prevalence (percentage) of patients with related gastrointestinal side effects and nonvertebral fracture rates did not differ significantly between the combined SR-NaF group and the Placebo group (hip fracture rate of 0.0045/patient year in SR-NaF and 0.0053/patient year in Placebo; appendicular fracture other than hip (see text) rate of 0.0193/patient year in SR-NaF and 0.0159/patient year in Placebo). A subgroup analysis showed a low baseline L2-L4 BD, high prevalent spinal fractures, and reduced body weight to be important determinants of the development of spinal fracture during SR-NaF treatment. Concomitant medications (estrogen, vitamin D, thiazide and thyroid hormone) were not independent predictors of the spinal fracture risk. Only 17% of fluoride-treated patients were nonresponders (new spinal fractures or a fall/no change in L2-L4 bone mass). Thus, the effects of SR-NaF treatment on the spinal fracture rate from nonrandomized trials were similar to those of the treated group of the randomized trial but different from those of the Placebo group. The similarity of response of nonrandomized trials with that of the randomized controlled trial and the resultant combined analysis further validate the efficacy and safety of SR-NaF in the treatment of postmenopausal osteoporosis.

Bone Density↗
PubMed1996

Quantitation of incident spinal fractures: comparison of visual detection with quantitative morphometry.

The value of quantitative morphometry in detection of new spinal fractures was assessed in serial radiographs from 83 patients with osteoporosis. From vertebral landmarks on lateral spine radiographs, a computer program allowed calculation of vertebral heights and area. By comparing vertebral dimensions in the two sets of films, incident spinal fractures could be quantitated based either on the minimum criteria of 15% reduction in vertebral height (CM2) or a fall in height and area of 20% and 10% (CM1). The results of quantitative morphometry were compared with those of the consensus and individual readings of visual detection by three experienced investigators in the same paired sets of spinal films. For incident new fractures, the visual consensus method (V-C) showed a very good agreement with individual visual detection (kappa of 0.794 to 0.916) as well as with CM1 (kappa of 0.821). However, there was a poor agreement between the results of consensus reading and of detection by CM2 (kappa of 0.341), due to excessive number of fractures identified by CM2, but not by the visual method. For incident recurrent fractures, there was a poor agreement between V-C and individual visual detection, and between V-C and quantitative morphometry (kappa of 0.306 to 0.496). It was due to severe compression fractures at baseline, which caused further changes in vertebral dimensions difficult to measure accurately by either visual or quantitative morphometry. Thus, if the visual detection of fractures by a consensus of experienced investigators is considered as the "gold standard," quantitative morphometry, based on minimum reduction in vertebral height of 20% accompanied by a minimum decline in area of 10%, provides an objective detection of incident new spinal fractures but not of recurrent fractures.

Aged↗
PubMed1996

The lack of influence of long-term potassium citrate and calcium citrate treatment in total body aluminum burden in patients with functioning kidneys.

BACKGROUND: It has been suggested that citrate salts might enhance aluminum (Al) absorption from a normal diet, posing a threat of Al toxicity even in subjects with normal renal function. We have recently reported that in normal subjects and patients with moderate renal failure, short-term treatment with tricalcium dicitrate (Ca3Cit2) does not significantly change urinary and serum Al levels. However, we have not assessed total body Al stores in patients on long-term citrate treatment. OBJECTIVE: The objective of this study was to ascertain body content of Al non-invasively using the increment in serum and urinary Al following the intravenous administration of deferoxamine (DFO) in patients with kidney stones and osteoporotic women undergoing long-term treatment with potassium citrate (K3Cit) or Ca3Cit2, respectively. METHODS: Ten patients with calcium nephrolithiasis and five with osteoporosis who were maintained on potassium citrate (40 mEq/day or more) or calcium citrate 800 mg calcium/day (40 mEq citrate) for 2 to 8 years, respectively, and 16 normal volunteers without a history of regular aluminum-containing antacid use participated in the study. All participants completed the 8 days of study, during which they were maintained on their regular home diet. Urinary Al excretion was measured during a two-day baseline before (Days 5, 6) and for 1 day (Day 7) immediately following a single intravenous dose of DFO (40 mg/kg). Blood for Al was obtained before DFO administration, and at 2, 5 and 24 hours following the start of the infusion. RESULTS: The median 24-hour urinary Al excretion (microgram/day) at baseline versus post-DFO value was 15.9 vs. 44.4 in the normal subjects and 13.3 vs. 35.7 in the patients. These values were all within normal limits and did not change significantly following DFO infusion (p = 0.003 and p = 0.0001, respectively). The median change of 17.1 micrograms/day in urinary Al in the normal subjects was not significantly different from the 18.7 micrograms/day change measured in the patient group (p = 0.30). Similarly, no change in the mean serum Al was detected at any time following the DFO infusion, either in the patient or control group (patients 4.1 to 4.3 ng/ml, controls 7.4 to 4.6 ng/ml). CONCLUSION: The results suggest that abnormal total body retention of Al does not occur during long-term citrate treatment in patients with functioning kidneys.

Adult↗
PubMed1996

Recent advances in the biochemical and molecular biological basis of cystinuria.

PURPOSE: We reviewed the literature describing recent advances in the understanding of the nature of the transport proteins involved in the renal transport of cystine, properties of the solute carrier family 3, member 1 (SLC3A1) gene, which is involved in renal cystine transport, and the mutations reported in this gene, which have been shown to be the causative factor in approximately half of the cases of type I cystinuria studied. MATERIALS AND METHODS: The MEDLINE data base from 1966 to date and the internet online mendelian inheritance in man were searched using cystinuria, cystine crossed with biological transporters and cystine transporter as key words. Selected citations within these references were also reviewed. RESULTS: The SLC3A1 gene has been shown to code for a protein that, when expressed in Xenopus oocytes, confers on these cells the ability to transport cystine, arginine, lysine and ornithine. To date 21 different mutations and 9 polymorphisms have been reported in the SLC3A1 gene isolated from cystinuric patients. CONCLUSIONS: Type I cystinuria appears to be due to mutations in the SLC3A1 gene, while the molecular genetic determinants of types II and III cystinuria remain to be delineated.

Amino Acid Transport Systems, Basic↗
PubMed1995

Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final report of a randomized controlled trial.

OBJECTIVE: To test whether slow-release sodium fluoride inhibits spinal fractures and is safe to use. DESIGN: Placebo-controlled randomized trial. INTERVENTIONS: Slow-release sodium fluoride, 25 mg twice daily, in four 14-month cycles (12 months receiving sodium fluoride followed by 2 months not receiving it) compared with placebo. Calcium citrate, 400 mg calcium twice daily, continuously in both groups. PATIENTS: 48 of 54 patients who received sodium fluoride and 51 of 56 patients who received placebo completed at least 1 year of the study. All patients had postmenopausal osteoporosis. RESULTS: Compared with the placebo group, the fluoride group had a lower individual vertebral fracture rate (0.064 +/- 0.182 per patient-year compared with 0.205 +/- 0.297 per patient-year; P = 0.002), a higher unadjusted fracture-free rate (85.4% compared with 56.9%; P = 0.001), and a greater survival estimate (relative risk, 0.3 [95% CI, 0.12 to 0.76]) for new fractures. The recurrent spinal fracture rate did not differ between the two groups. The fluoride group had a substantial increase in L2-L4 bone mass of 4% to 5% per year for 4 years, a mean increase in femoral neck bone density of 2.38% +/- 3.33% per year, and no change in radial shaft bone density. The frequency with which minor side effects and appendicular fractures occurred was similar in the two groups; no patients developed microfractures or gastric ulcers. CONCLUSION: Slow-release sodium fluoride and calcium citrate administered for 4 years inhibits new vertebral fractures (but not recurrent fractures), augments spinal and femoral neck bone mass, and is safe to use.

Aged↗
PubMed1995

Physicochemical effects of a new slow-release potassium phosphate preparation (UroPhos-K) in absorptive hypercalciuria.

A new slow-release, neutral potassium phosphate salt (UroPhos-K) has been formulated in order to minimize gastrointestinal side effects and avoid sodium-induced calciuria. It was tested in a prospective randomized, double-blind trial in a group of 21 kidney stone patients with absorptive hypercalciuria type I (AH). Twelve patients allocated to the UroPhos-K group received four tablets twice daily with breakfast and an evening snack providing 1240 mg of phosphorus and 63.5 mEq of potassium daily. Nine patients assigned to the placebo group received placebo tablets of the same appearance containing excipient only. Subjects were studied during a 3-day period in the hospital while consuming a constant metabolic diet containing 400 mg Ca, 100 mEq Na, and 800 mg P per day before and after 3 months of treatment. Treatment with UroPhos-K did not cause any significant gastrointestinal side effects; nor did it raise fasting serum K or phosphorus, or reduce hemoglobin or creatinine clearance. It was associated with a rise in urinary K from 46 +/- 7 to 98 +/- 9 mEq per day and phosphorus from 744 +/- 185 to 1535 +/- 112 mg per day (p < 0.001 each). UroPhos-K treatment reduced urinary Ca from 288 +/- 63 to 171 +/- 49 mg/day (p < 0.001), without altering oxalate excretion. It reduced the urinary saturation of calcium oxalate without altering that of brushite. Moreover, by increasing urinary excretion of inhibitors (citrate and pyrophosphate), it reduced the propensity for spontaneous nucleation of brushite (increased formation product of brushite) and inhibited crystal agglomeration of calcium oxalate.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Prevention of hypercalciuria and stone-forming propensity during prolonged bedrest by alendronate.

The bone loss and hypercalciuria induced by immobilization or the decreased gravitational forces of space are well described. Using a model of bedrest immobilization, the ability of a potent aminobisphosphonate, alendronate, to avert hypercalciuria and stone-forming propensity was tested. Sixteen male subjects participated in a randomized, placebo-controlled trial in which they received either 20 mg of alendronate or placebo 2 weeks prior to and during 3 weeks of strict bedrest. Parameters of bone and calcium metabolism and urinary crystallization of stone-forming salts were measured before and at the end of bedrest. In the placebo group, bedrest increased urinary calcium (209 +/- 47 to 267 +/- 60 mg/day, p < 0.01) and the saturation of calcium phosphate. Before bedrest, the alendronate group had a significantly lower serum calcium (8.8 +/- 0.4 vs. 9.6 +/- 0.5 mg/dl, p < 0.01) and higher serum PTH (62.4 +/- 33.1 vs. 23.1 +/- 7.5 pg/ml, p < 0.01) compared with the placebo group. Moreover, the alendronate group had a lower urinary calcium (75 +/- 41 mg/day) and saturation of calcium oxalate and calcium phosphate. These effects of alendronate were sustained during bedrest. Following bedrest in the alendronate group, urinary calcium rose to 121 +/- 50 mg/day, a value less than that in the placebo group before or during bedrest. Similarly, urinary saturation of calcium oxalate and calcium phosphate rose with bedrest in the alendronate-treated patients but remained lower than values obtained in placebo-treated patients before or during bedrest. Alendronate inhibits bone mineral loss and averts the hypercalciuria and increased propensity for the crystallization of stone-forming calcium salts which occurs during 3 weeks of strict bedrest.

Adult↗
PubMed1995

Serum IGF 1 is low and correlated with osteoblastic surface in idiopathic osteoporosis.

We have previously reported that bone formation is impaired on histomorphometric analysis of bone in patients with idiopathic osteoporosis. In the present study, 30 patients with idiopathic osteoporosis (18 men and 12 women mean age 44 +/- 12 years) and spinal and/or appendicular fractures were studied. Compared with control values, bone biopsy analysis demonstrated reduced bone volume (13.0 +/- 4.4 vs. 23.2 +/- 4.4, p < 0.0001), osteoid volume (0.13 +/- 0.13 vs. 0.32 +/- 0.19, p = 0.001), osteoid surface (5.9 +/- 4.3 vs. 12.1 +/- 4.6, p = 0.0004), and diminished double-labeled mineralizing surface (MS/BS 2.0 +/- 2.1 vs. 5.1 +/- 2.7%, p = 0.0001) in the patients. Since insulin-like growth factor 1 (IGF-1) is one of the major determinants of bone growth and remodeling, we measured the circulating level of this growth factor in these patients. The mean serum IGF-1 concentration was lower in patients as compared with 33 healthy age-matched controls (193 +/- 59 SD ng/ml vs. 232 +/- 79). A significant difference was noted between the two groups only in subjects younger than 36 years. In patients with idiopathic osteoporosis, regression analysis of serum IGF-1 against the various histological parameters measured from the bone biopsy disclosed significant correlation's between serum IGF-1 and osteoblastic surface (r = 0.429, p = 0.032), mineralizing bone surface with a double label (r = 0.480, p = 0.015), and the bone formation rate (r = 0.457, p = 0.021). These findings suggest that in young eugonadal individuals with idiopathic osteoporosis, reduced IGF-1 concentrations may have an etiological role in the development of this disease.

Adult↗
PubMed1995

Ambulatory evaluation of nephrolithiasis: an update of a 1980 protocol.

Evaluations of 1,270 patients with recurrent nephrolithiasis in an outpatient setting were analyzed for the purpose of updating the classification of nephrolithiasis. All but 4% had abnormal urinary biochemistry that placed them into one or more of 20 etiologic categories. A single diagnosis was documented in 41.3% of patients. The remaining 58.7% had more than one diagnosis. Hypercalciuric calcium (Ca) nephrolithiasis, encountered in 60.9% of patients, comprised six variants--absorptive hypercalciuria Type I and II, renal hypercalciuria, primary hyperparathyroidism, and unclassified hypercalciuria (renal phosphate leak and fasting hypercalciuria). Hyperuricosuria Ca nephrolithiasis (HUCN) and gouty diathesis (GD) accounted for 35.8% and 10.0% of patients, respectively. Distinguishing features were hyperuricosuria and normal urinary pH in HUCN, and normal urinary uric acid and low urinary pH (< 5.5) in GD. Hyperoxaluric Ca nephrolithiasis, occurring in 8.1% of patients, was subdivided into enteric, primary, and dietary variants. Hypocitraturic Ca nephrolithiasis affected 28% of patients in its idiopathic variant. Many of these patients' problems were probably dietary in origin, while some could have had incomplete renal tubular acidosis. Hypocitraturia due to renal tubular acidosis or chronic diarrheal syndrome affected only 3.3% of patients. Hypomagnesiuric Ca nephrolithiasis, infection stones, and cystinuria were uncommon, accounting for 6.8%, 5.9%, and 0.9% of patients, respectively. The acquired problem of low urine volume (< 1 L/d) was found in 15.3% of patients. The remaining 3.5% of patients were difficult to classify despite the presence of abnormal urinary biochemistry.

Adult↗
PubMed1995

Clinical and biochemical presentation of gouty diathesis: comparison of uric acid versus pure calcium stone formation.

PURPOSE: We compared gouty diathesis with uric acid versus calcium stones. MATERIALS AND METHODS: We retrospectively reviewed clinical and laboratory data from 95 gouty diathesis patients (28 with uric acid and 67 with calcium stones) and 99 normal subjects. RESULTS: Of the gouty diathesis patients gouty arthritis was present in 21% of those with uric acid and 12% of those with calcium stones. Hyperuricemia developed in 43% of those with uric acid and 27% of those with calcium stones, and 2% of controls. Urinary pH was independent of the net gastrointestinal absorption of alkali in the gouty diathesis groups. Urinary pH and citrate increased after potassium citrate treatment. CONCLUSIONS: The characteristic features of primary gout were present in both gouty diathesis groups and both are responsive to treatment.

Adult↗
PubMed1995

Effect of medical management and residual fragments on recurrent stone formation following shock wave lithotripsy.

Minimal emphasis has been placed on the clinical sequelae of residual stone fragments following shock wave lithotripsy. Moreover, there are no studies investigating the role of medical therapy on the course of stone disease in patients with residual fragments. In this retrospective, nonrandomized review, we evaluated 80 patients who had undergone shock wave lithotripsy at various institutions in Texas and were referred to our mineral metabolism clinic for metabolic evaluation and medical management of the stone disease. Of the patients 31 were determined to be stone-free following lithotripsy, while 49 had residual stone fragments. All patients were contacted an average of 43.2 months (range 9 to 79) following shock wave lithotripsy and the radiographs were reviewed. Patients were placed into 4 groups after shock wave lithotripsy: stone-free or residual fragments on or off medical therapy. In the stone-free group (19 patients), medical treatment produced a significant decrease in stone formation from a median of 0.67 to 0.0 stones per patient per year (p < 0.001). In 36 patients with residual fragments stone formation before shock wave lithotripsy was higher than in the stone-free group but there was also a significant decrease in the stone formation rate from a median of 2.47 to 0.00 stones per patient per year while on medical therapy (p < 0.001). Of the 12 stone-free patients who did not remain on medical therapy there was a slight decrease in the stone formation rate from a mean of 0.83 to 0.40 stones per patient per year, although this decrease was not significant (p = 0.07). In 13 patients with residual fragments not on medical treatment there was only a minimal decrease in the stone formation rate from a median of 1.33 to 0.77 stones per patient per year (p = 0.06). We also assessed the significance of so-called clinically insignificant residual fragments (smaller than 5 mm.) following shock wave lithotripsy in 26 of the 36 patients with residual fragments. More than half of the 26 patients with clinically insignificant fragments in the group that did not continue on medical therapy demonstrated significant stone growth during followup, suggesting that these fragments were not insignificant. Moreover, only 16% of the patients with fragments smaller than 5 mm. demonstrated an increase in fragment size while on medical therapy, again suggesting that appropriate medical treatment can decrease the risk of recurrent stone formation or growth (p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Cloning and expression of the VP1 major capsid protein of diabetogenic encephalomyocarditis (EMC) virus and prevention of EMC virus-induced diabetes by immunization with the recombinant VP1 protein.

The development of diabetes in mice induced by encephalomyocarditis (EMC) virus provides the best experimental evidence that viruses have an aetiological role in the pathogenesis of this disease. The major capsid protein (VP1) of EMC virus is important for both the attachment of the virus to pancreatic beta cells and for the determination of antigenicity. This experiment was initiated to clone the gene for the major capsid protein, VP1, of the diabetogenic EMC (EMC-D) virus, express the VP1 protein, and test whether the recombinant VP1 protein can prevent development of EMC-D virus-induced diabetes in mice. We successfully cloned the VP1 gene of the EMC-D virus in the expression vector pRSET and subsequently expressed the protein in Escherichia coli. The recombinant VP1 protein was then purified by affinity chromatography. Five- to six-week-old male SJL/J mice were immunized intraperitoneally with purified VP1 protein and then challenged after various intervals with highly diabetogenic EMC-D virus. None of the VP1-immunized mice developed diabetes, irrespective of the interval between immunization and virus challenge, whereas 80 to 95% of the EMC-D virus-infected control mice did develop diabetes. All of the VP1-immunized mice showed intact pancreatic islet architecture, whereas most of the infected control mice showed severe beta cell necrosis and lymphocytic infiltration of their pancreatic islets. On the basis of these observations, we conclude that the recombinant VP1 protein of EMC-D virus can completely prevent the development of EMC-D virus-induced diabetes in mice.

Amino Acid Sequence↗
PubMed1995

Evidence for normal vitamin D receptor messenger ribonucleic acid and genotype in absorptive hypercalciuria.

Absorptive hypercalciuria (a stone-forming condition) is characterized by gut hyperabsorption of calcium, hypercalciuria, and reduced bone density. Inasmuch as these features implicate enhanced calcitriol action in gut and bone, we analyzed the vitamin D receptor (VDR) gene to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium. We have compared the frequency of a restriction fragment length polymorphism (Bsm I) associated with different alleles of the VDR gene in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects. There was no difference between the distribution of the VDR alleles in the patient population when compared with the normal population. The coding region of VDR messenger RNA was also normal, as determined by both DNA sequence analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients. On the basis of these results, we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the VDR and are not linked to a common VDR genotype.

Alleles↗
PubMed1995

Beta cell-specific expression of retroviral mRNAs and group-specific antigen and the development of beta cell-specific autoimmunity in non-obese diabetic mice.

Non-obese diabetic (NOD) mice spontaneously develop autoimmune type 1 diabetes. Earlier studies have shown that retroviruses appear to be associated with the development of the disease in these animals. This investigation was initiated to determine whether any retroviral genes are specifically expressed in pancreatic beta cells from NOD mice, in contrast to their non-diabetic, parental strain, ICR mice. Host chromosomal DNAs from pancreatic islets, kidneys, hearts, and stomachs of NOD and ICR mice contained an equal amount of A-type retroviral genome (DNA); however, A-type retroviral gag, pol, and env mRNAs were detected in only the pancreatic islets from NOD mice. Furthermore, group-specific retroviral antigen (p73 of A-type--gag gene product) was found by immunofluorescent staining using anti-p73 antibody in only pancreatic beta cells from NOD mice. On the basis of these observations, we suggest that tissue and strain differences in transcription of the retroviral genome and beta cell-specific expression of A-type retroviral group-specific antigen p73 in NOD mice may be involved in the initiation of beta cell-specific autoimmunity leading to type 1 diabetes in these animals.

Animals↗
PubMed1994

Treating a patient with the Werner syndrome and osteoporosis using recombinant human insulin-like growth factor.

OBJECTIVE: To assess the safety and effect of recombinant human insulin-like growth factor 1 (rhlGF-1) on measures of bone metabolism in a human model of age-related osteoporosis. DESIGN: 6-month prospective case study. SETTING: General clinical research center. PATIENTS: 1 patient with the Werner syndrome, a low serum IGF-1 level, and osteoporosis. INTERVENTION: Daily subcutaneous administration of rhIGF-1 for 6 months. MEASUREMENTS: Serum alkaline phosphatase, osteocalcin, type I procollagen C-peptide and urinary hydroxyproline, calcium, and pyridinoline cross-links as measures of bone metabolism and radial shaft, femoral neck, and lumbar bone masses. RESULTS: Serum osteocalcin and type I procollagen C-peptide increased during rhIGF-1 therapy (P < 0.05). Twenty-four hour urinary calcium, hydroxyproline, and pyridinoline cross-links were also higher after treatment than they were before treatment (P < 0.05). During 6 months of treatment, the bone mineral density of the L2 to L4 vertebrae increased 3%; this value exceeded the coefficient of variation of this measurement. Bone density at the femoral neck and radial shaft changed by less than the coefficient of variation of these measurements. No significant changes in serum glucose values or other adverse effects of treatment were noted. CONCLUSIONS: Treatment with rhIGF-1 increased both bone formation and resorption in a patient with the Werner syndrome, a low baseline serum IGF-1 level, and established osteoporosis. Because lumbar bone mass increased without evidence of bone loss in the appendicular skeleton, a net increase in bone formation (formation greater than resorption) may have been responsible.

Adult↗