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Biomedical subjects

K W Lyles

Publications and source records attributed to K W Lyles.

At least 19 recordsLinked to original sources
PubMed1991

Uremic tumoral calcinosis: preliminary observations suggesting an association with aberrant vitamin D homeostasis.

Periarticular tumoral calcification is a unique form of soft tissue calcification that occurs infrequently in patients with end-stage renal disease. The mechanism underlying such massive periarticular calcifications is unknown. The radiographic similarity between uremic tumoral calcifications and those found in hereditary tumoral calcinosis, a disorder of calcitriol and phosphorus homeostasis, caused us to examine whether abnormalities in vitamin D metabolism were associated with uremic calcinosis as well. We examined two uremic subjects with massive periarticular tumoral calcifications and found that they had inappropriately high serum calcitriol levels for the degree of renal function, hyperparathyroidism, and hyperphosphatemia. The source of calcitriol could not be identified in one subject, but likely was derived from granulomatous tissue in the other. In the subject with marrow granulomas, we found that calcitonin administration further stimulated calcitriol production. Although epidemiological studies are needed to confirm this preliminary association between calcitriol and uremic tumoral calcinosis, our observations suggest that normal serum calcitriol levels in association with hyperphosphatemia may be a contributing factor in the development of this rare disorder.

Adult↗
PubMed1991

The metabolic effects of calcium supplementation in the elderly.

Because the value of calcium supplementation in age-related bone loss is controversial, we conducted a study to examine the effects of six months of calcium supplementation on parathyroid hormone (PTH) and other indices of bone metabolism. Calcium carbonate (1.2 grams elemental calcium/day) or placebo was administered for 6 months to a group of 42 healthy, ambulatory men and women with a mean age of 71. Fasting blood samples and 2-hour urine collections were performed at baseline and at 1 and 6 months. The decline in serum PTH levels from baseline in the calcium-supplemented group was significant in comparison with the placebo group changes (for the calcium group: 40.9 pg/mL at baseline to 34.0 pg/mL at 1 month and 33.2 at 6 months). This drop in PTH was associated with a decline in 1,25 OH-Vitamin D levels from a mean of 38.3 pg/mL to 30.4 pg/mL at 1 month and 31.9 at 6 months. During calcium supplementation, no changes were observed in serum bone Gla protein values. A decline in urinary hydroxyproline excretion was observed at 6 months, but this did not reach significant levels. The present study demonstrates suppression of PTH levels with calcium supplementation, an effect which lasts at least 6 months. This change was accompanied by a decrease in serum 1,25 OH-Vitamin D. The lack of significant changes in either serum bone gla protein or urine hydroxyproline excretion fails to support any significant change in bone turnover occurring with this decrease in PTH.

Administration, Oral↗
PubMed1991

Effects of short-term administration of glucocorticoids on bone metabolism in healthy elderly men.

OBJECTIVE: To determine the effects of short-term glucocorticoid administration in healthy elderly men on bone GLA protein (BGP) levels, as well as levels of calcium, phosphorus, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase. DESIGN: Subjects served as own control before and after prednisone treatment. SETTING: Male subjects were recruited by telephone from the Duke University Aging Center Volunteer Registry and the Department of Veterans Affairs Medical Center Gerofit Program (a supervised exercise program). PARTICIPANTS: Healthy males age greater than 60 years with no history of diabetes mellitus, glucose intolerance, or prior glucocorticoid use. Subjects could not be taking diuretic agents and could not have osteoporosis. The seven subjects mean age +/- std dev was 68.6 +/- 5.3 years. INTERVENTIONS: Prednisone 40 mg orally for 5 days. Fasting serum was obtained at baseline, on days 7 through 11, 13, 15, and 17. Assays of BGP, calcium, phosphorus, PTH, and alkaline phosphatase were performed. MAIN OUTCOME MEASURES: Changes in serum BGP levels was the primary outcome measure. Changes in serum calcium, phosphorus, PTH, and alkaline phosphatase levels were secondary outcome measures. RESULTS: Treatment caused reduction in BGP levels within 24 hours of first dose of prednisone, with levels dropping an average of 78% during the 5 days of treatment (P = 0.004). Within 24 hours of stopping treatment, BGP was no different from baseline. Other variables did not change with treatment. CONCLUSION: Glucocorticoid treatment suppresses BGP production in healthy elderly men in the same fashion as it does in younger healthy men.

Administration, Oral↗
PubMed1991

Osteoporosis in late life: does health locus of control affect psychosocial adaptation?

Osteoporosis, a metabolic bone disease most prevalent in older adults, is a major public health problem. Although management of osteoporosis through diet, exercise, and medication has improved, little is known about the psychosocial consequences of this disabling disease. In an attempt to identify patient characteristics that would provide physicians with insight into appropriate management styles for older osteoporotics, we assessed 103 patients with osteoporosis for their health locus of control (HLOC) orientation. We examined the relationship between HLOC and patient outcomes after participation in the Duke University Preventive and Therapeutic Program for Osteoporosis (DUPATPO) to determine whether HLOC was associated with functioning after program participation. More specifically, we asked whether internal or external HLOC was associated with decreases in depression, psychiatric symptoms, and stress symptoms, or with increases in self-esteem, exercise, and disease knowledge. We have shown in our earlier work (Gold et al, J Am Geriatr Soc 1989; 37:417) that program participation is associated with improved functioning in older adults. We now asked whether knowledge of a patient's HLOC would help predict these improvements. A comparison group (ie, older osteoporotics who did not participate in DUPATPO) was also assessed for HLOC to examine the possible association between HLOC and health behaviors regardless of the DUPATPO intervention. Our findings indicate that HLOC provided little useful information regarding patient outcomes. Although improvements were seen in the mental health of program participants, no association between these improvements and HLOC could be found.

Adaptation, Psychological↗
PubMed1991

Dental lesions in tumoral calcinosis.

Tumoral calcinosis (TC) is a rare inherited autosomal dominant metabolic disease manifested by elevated serum phosphorus and 1,25 dihydroxyvitamin D levels and periarticular cystic and solid tumorous calcifications. The dental findings in a large family have been critical in determining the genetic transmission of the condition. Radiographically the teeth have short bulbous roots, pulp stones and partial obliteration of the pulp cavity. Histologically, coronal dentin and a variable amount of radicular dentin appears to be deposited regularly. At nonspecific points the developing radicular dentin appears to encounter a mass of calcified material and proceed to grow around it. This mass has a unique histologic pattern with ovoid spaces surrounded by amorphous calcification. At levels of further root development the radicular dentin has an irregular bending tubule arrangement. The dental lesion of TC appears to be different from that of radicular dentin dysplasia in histologic structure and in the method of initiation of the dentin defect. These data suggest that the specific dental lesion is a new phenotypic marker for TC.

Adolescent↗
PubMed1990

Glucocorticoid-induced osteoporosis: mechanisms for bone loss; evaluation of strategies for prevention.

Osteoporosis is a common complication of chronic glucocorticoid therapy, especially in older patients who already are at risk of having a reduced bone mass. Glucocorticoids cause bone loss by altering the bone remodeling sequence: bone resorption by osteoclasts is increased, and bone formation by osteoblasts is decreased. Serum levels of osteocalcin, a protein made by osteoblasts, are decreased with glucocorticoid therapy, further evidence of decreased osteoblast function. Glucocorticoids decrease calcium absorption by the gastrointestinal tract and increase renal calcium excretion. Several recent studies suggest that low-dose glucocorticoid therapy is not associated with bone loss. Calcium supplementation with vitamin D is recommended. Several short-term studies have shown prevention of glucocorticoid-induced bone loss with bisphosphonates, calcitonin, and progesterone. Long-term clinical trials should be undertaken to determine strategies to prevent this type of osteoporosis.

Aged↗
PubMed1990

Calcium supplementation lowers serum parathyroid hormone levels in elderly subjects.

To determine the effect of calcium supplementation on parathyroid hormone levels (PTH) in a group of elderly subjects at risk for developing Type II (senile) osteoporosis, 40 healthy volunteers participated in a randomized double-blind crossover study. Calcium carbonate or placebo was administered for 4 weeks, followed by a 4-week administration of the alternative intervention. Fasting blood samples and 24-hour urine collections were obtained at baseline, and at the end of each intervention period. Calcium supplementation (1000 mg/day) decreased serum PTH levels from a mean of 50.1 +/- 3.0 pg/ml to 41.9 +/- 2.4 pg/ml (p less than .001). Additionally, urine calcium excretion significantly increased during calcium administration (from 3.64 mmol/mmol creatinine at baseline to 4.28 mmol/mmol creatinine), but creatinine clearances and serum calcium levels remained unchanged. Type II osteoporosis has been associated with age-related increases in PTH levels. We have demonstrated the ability of increased calcium intake to decrease these levels, which may have implications for the management of a subset of patients with involutional osteoporosis.

Aging↗
PubMed1990

Imaging of tumoral calcinosis: new observations.

Five patients with tumoral calcinosis were evaluated with radiography, bone scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging. The arthropathy of calcium pyrophosphate dihydrate deposition disease was seen in two of the patients and pseudoxanthoma elasticum-like syndrome in three. Identification of calcific particular masses on radiographs is characteristic of tumoral calcinosis. Marrow lesions could be identified as patchy areas of calcification (calcific myelitis) in long bones and the calvarium. Bone scintigraphy appears to be the best modality for detection of the masses and marrow lesions and for monitoring therapy. At CT the masses demonstrated a varied appearance, from small and solid to large and cystic. The marrow abnormality appears as an area of increased attenuation and spotty calcification that in the skull may be associated with dural and vascular calcifications. MR imaging of the particular masses was remarkable in that the masses displayed high signal intensity on T2-weighted images despite a large calcific component. Marrow lesions also showed increased signal intensity on T2-weighted images. When calcified particular masses are present the diagnosis is rarely in question. The diagnosis may be overlooked, however, when calcific myelitis is the only manifestation.

Adult↗
PubMed1989

Geriatrics.

Explore the source record for details and available documents.

Age Factors↗
PubMed1989

Treatment of osteoporosis. The psychological impact of a medical education program on older patients.

Participants in a therapeutic program for osteoporosis were studied to determine if program participation improved psychological outcomes. The 4-day program included intensive education about the disease and its prognosis, physical therapy education, nutritional counseling, and medical evaluation and treatment. All therapeutic patients enrolled in the program over a one-year period (N = 38) were interviewed individually pre- and post-participation. Knowledge of osteoporosis, level of social support, coping styles, and perceptions of the impact of pain and chronicity were assessed. Patients reported improved future outlook despite continued concern about pain and chronicity. Mention of depression was reduced, and knowledge of osteoporosis increased significantly. In addition, there were meaningful changes in patients' understanding of disease management. These included knowing when to make specific changes and avoid harmful actions. The findings suggest that an educational program can have a positive impact on patients' coping. Educational efforts may be an important component in the management of chronic disease.

Adaptation, Psychological↗
PubMed1988

Correlations of serum concentrations of 1,25-dihydroxyvitamin D, phosphorus, and parathyroid hormone in tumoral calcinosis.

The inherited metabolic disorder tumoral calcinosis is characterized by elevated serum phosphorus and 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels and paraarticular calcific tumors. The pathogenesis of this disease is obscure, but an elevated renal phosphate reabsorption threshold and increased production of 1,25-(OH)2D are postulated as defects. We studied nine affected patients and found that both serum phosphorus and renal phosphate reabsorption threshold (TmP/GFR) were positively correlated with serum 1,25-(OH)2D levels. Since tumoral calcinosis is a disorder with abnormal renal phosphate transport, we compared the TmP/GFR and serum 1,25-(OH)2D levels to values obtained in patients with two other diseases with renal phosphate transport defects: oncogenic osteomalacia and X-linked hypophosphatemic rickets. We found a significant correlation between TmP/GFR and 1,25-(OH)2D levels in all three diseases, suggesting that in these diseases 1,25-(OH)2D production is regulated in some manner by phosphate transport. Furthermore, previous work indicated that in tumoral calcinosis broad variation exists in serum phosphorus levels. In our patients a negative correlation was found between the serum PTH concentrations and both serum phosphorus levels and TmP/GFR values, respectively. We postulate that although the basic defect in tumoral calcinosis most likely resides in the proximal renal tubular cell, the variation in serum phosphorus levels and possibly disease expression is modulated in part by PTH.

Absorption↗
PubMed1987

Skeletal disorders in malignant disease.

When the elderly are afflicted by malignancy, chances are good that at some point in the course of their illness the skeleton will be involved. Bone metastases, hypercalcemia, and other paraneoplastic syndromes are commonly encountered and require definitive diagnosis and management. In general, the therapy for the elderly patient with these disorders is the same as that for younger individuals. The diagnostic and therapeutic approach must often be tempered, however, by coexistent chronic disease, which may also affect the skeleton.

Aged↗
PubMed1987

What is the clinical significance of bone loss in primary hyperparathyroidism?

To help determine the clinical significance of the bone loss associated with primary hyperparathyroidism, we studied the prevalence of vertebral fractures in a group of patients with this disorder. From a registry of parathyroidectomies, 206 cases were reviewed, and lateral chest roentgenograms were studied for the presence of fractures. All roentgenograms were interpreted by two of the investigators who were "blinded" to diagnoses. Comparisons of readings were made that assured interrater agreement. A group of patients who underwent cholecystectomy served as controls. Studied in a logistic regression analysis model, controlling for the effects of age, sex, and race, primary hyperparathyroidism was found to be significantly associated with vertebral fractures. Subgroup analyses performed on the patients with hyperparathyroidism failed to identify specific biochemical or clinical markers associated with fractures. Our results suggest that the bone loss of primary hyperparathyroidism is clinically significant, leading not only to decreased bone densities but also to an increased prevalence of fractures.

Adult↗
PubMed1985

Calcification of entheses associated with X-linked hypophosphatemic osteomalacia.

We undertook a retrospective analysis of 26 patients with X-linked hypophosphatemic osteomalacia (or rickets), whose ages ranged from 1 to 62 years and who were from 11 different kindreds, to determine the prevalence and clinical characteristics of a unique disorder of the entheses (tendons, ligaments, and joint capsules). We found a generalized involvement of the entheses, with exuberant calcification of tendon and ligament insertions and of joint capsules, in 69 per cent of the subjects. The prevalence and extent of disease increased with age but were not correlated with sex. Commonly affected sites included the hand and sacroiliac joints. Histologic evaluation in a selected patient revealed intratendinous lamellar bone but no inflammatory cells. Our observations indicate that this disorder is an integral part of X-linked hypophosphatemic osteomalacia and exhibits clinical, radiographic, and histologic characteristics that differentiate it from degenerative disorders of these tissues and seronegative spondyloarthropathies.

Adolescent↗
PubMed1985

Healing of bone disease in X-linked hypophosphatemic rickets/osteomalacia. Induction and maintenance with phosphorus and calcitriol.

Although conventional therapy (pharmacologic doses of vitamin D and phosphorus supplementation) is usually successful in healing the rachitic bone lesion in patients with X-linked hypophosphatemic rickets, it does not heal the coexistent osteomalacia. Because serum 1,25-dihydroxyvitamin D levels are inappropriately low in these patients and high calcitriol concentrations may be required to heal the osteomalacia, we chose to treat five affected subjects with high doses of calcitriol (68.2 +/- 10.0 ng/kg total body weight/d) and supplemental phosphorus (1-2 g/d) performing metabolic studies and bone biopsies before and after 5-8 mo of this therapy in each individual. Of these five patients, three (aged 13, 13, and 19 yr) were receiving conventional treatment at the inception of the study and therefore showed base-line serum phosphorus concentrations within the normal range. The remaining two untreated patients (aged 2 and 37 yr) displayed characteristic hypophosphatemia before calcitriol therapy. All five patients demonstrated serum calcitriol levels in the low normal range (22.5 +/- 3.2 pg/ml), impaired renal phosphorus conservation (tubular maximum for the reabsorption of phosphate per deciliter of glomerular filtrate, 2.13 +/- 0.20 mg/dl), and osteomalacia on bone biopsy (relative osteoid volume, 14.4 +/- 1.7%; mean osteoid seam width, 27.7 +/- 3.7 micron; mineral apposition rate, 0.46 +/- 0.12 micron/d). On high doses of calcitriol, serum 1,25-dihydroxyvitamin D levels rose into the supraphysiologic range (74.1 +/- 3.8 pg/ml) with an associated increment in the serum phosphorus concentration (2.82 +/- 0.19 to 3.78 +/- 0.32 mg/dl) and improvement of the renal tubular maximum for phosphate reabsorption (3.17 +/- 0.22 mg/dl). The serum calcium rose in each patient while the immunoactive parathyroid hormone concentration measured by three different assays remained within the normal range. Most importantly, repeat bone biopsies showed that high doses of calcitriol and phosphorus supplements had reversed the mineralization defect in all patients (mineral apposition rate, 0.88 +/- 0.04 micron/d) and consequently reduced parameters of bone osteoid content to normal (relative osteoid volume, 4.1 +/- 0.7%; mean osteoid seam width, 11.0 +/- 1.0 micron). Complications (hypercalcemia and hypercalciuria) ensued in four of these five patients within 1-17 mo of documented bone healing, necessitating reduction of calcitriol doses to a mean of 1.6 +/- 0.2 micrograms/d (28 +/- 4 ng/kg ideal body weight per day). At follow-up bone biopsy, these four subjects continued to manifest normal bone mineralization dynamics (mineral apposition rate, 0.88 +/-0.10 micrometer/d) on reduced doses of 1.25-dihydroxyvitamin D with phosphorus supplements (2 g/d) for a mean of 21.3 +/- 1.3 mo after bone healing was first documented. Static histomorphometric parameters also remained normal (relative osteoid volume, 1.5 +/- 0.4%; mean osteoid seam width, 13.5 +/- 0.8 micrometer). These data indicate that administration of supraphysiologic amounts of calcitriol, in conjunction with oral phosphorus, results in complete healing of vitamin D resistant osteomalacia in patients with X-linked hypophosphatemic rickets. Although complications predictably require calcitriol dose reductions once healing is achieved, continued bone healing can be maintained for up to 1 yr with lower doses of 1,25-dihydroxyvitamin D and continued phosphorus supplementation.

Adolescent↗