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Biomedical subjects

P C Kao

Publications and source records attributed to P C Kao.

At least 19 recordsLinked to original sources
PubMed1997

Urinary free cortisol and cortisone determined by high performance liquid chromatography in the diagnosis of Cushing's syndrome.

To determine the efficacy of cortisol and its metabolite, cortisone, measured simultaneously by high performance liquid chromatography (HPLC) in the diagnosis of Cushing's syndrome, we retrospectively reviewed the histories of 29 surgically proven Cushing's syndrome patients (20 Cushing's disease, 5 ectopic ACTH syndrome, and 4 adrenal Cushing's syndrome) and 6 patients with exogenous Cushing's syndrome. These 35 patients had urinary free cortisol determined by both HPLC and competitive binding methods. The efficacy of the HPLC assay using cortisol alone was equivalent to that of the competitive binding assay; 22 of 29 (76%) patients had increased cortisol. Cortisone also aided in the diagnosis; 25 of 29 (86%) had increased cortisone. Twenty-seven of the 29 (93%) patients had either both cortisone and cortisol (n = 19) or at least 1 of the 2 (n = 8) increased. All 6 patients with exogenous Cushing's syndrome had suppressed urinary free cortisol, cortisone, and the presence of prednisone and prednisolone. In the competitive binding assay, all exogenous Cushing's patients had falsely increased cortisol results. In conclusion, urinary free cortisol plus cortisone determined simultaneously by HPLC added a new dimension to the diagnosis of Cushing's syndrome. It should be considered when exogenous Cushing's syndrome is suspected or when only one urinary cortisol test is allowed to be ordered.

ACTH Syndrome, Ectopic↗
PubMed1997

Increased parathyroid hormone-related peptide in patients with hypercalcemia associated with islet cell carcinoma.

OBJECTIVE: To report the high prevalence of increased parathyroid hormone-related peptide (PTHrP) in patients with islet cell carcinoma and associated hypercalcemia. DESIGN: We conducted a retrospective study of PTHrP levels in patients with hypercalcemia and eucalcemia associated with islet cell carcinoma and compared these findings with those in healthy subjects. MATERIAL AND METHODS: Using a sensitive PTHrP immunochemiluminometric assay, we measured PTHrP levels in 17 patients with islet cell carcinoma and 110 healthy subjects. The differences between PTHrP levels in patients with normal and those with high serum calcium concentrations were analyzed statistically. RESULTS: PTHrP levels were significantly higher (P < 0.01) in 10 patients with hypercalcemia and islet cell carcinoma (median, 14.0 pmol/L; range, undetectable to 40.1) than in 7 patients with eucalcemia and islet cell carcinoma (median, undetectable; range, undetectable to 1.3 pmol/L) or in the 110 healthy subjects (median, undetectable; range, undetectable to 4.2 pmol/L). The range of increased PTHrP levels in hypercalcemic islet cell carcinoma was 2 to 20 times the upper normal limit (2.0 pmol/L). Decreased PTHrP and serum calcium and increased parathyroid hormone levels were demonstrated in two patients after effective therapy. For all seven eucalcemic patients with islet cell carcinoma, PTHrP levels did not differ significantly from those in healthy subjects. CONCLUSION: PTHrP levels are increased in a substantial proportion of patients with hypercalcemia and islet cell carcinoma and seem to decrease after treatment of the underlying tumor. Measurement of PTHrP levels may be useful for confirming the diagnosis of hypercalcemia associated with malignant disease and for monitoring of therapy.

Adult↗
PubMed1996

Three-year controlled, randomized trial of the effect of dose-specified loading and strengthening exercises on bone mineral density of spine and femur in nonathletic, physically active women.

The objectives of this study were to evaluate (1) the effect of spinal muscle strengthening by loading exercises on the bone mineral density (BMD) of the spine, and (2) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy, premenopausal women. The study design was a randomized, controlled trial of 3 years' duration. Ninety-six healthy, premenopausal, white women aged 30-40 years participated; 67 completed the study. All subjects were in good health (normal menses) and were active, but not athletic (that is, not involved in a regular sport activity). Subjects were randomized to an exercise or control group. The exercise group performed a supervised, non-strenuous, weight-lifting exercise program. Exercise performance was supervised once a week at the medical facility. In addition, the subjects performed the exercises twice a week on their own. Dietary calcium intake was to be maintained at 1,500 mg/day in both groups. Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0, 1, and 3 years. BMD of the midradius was measured with single photon absorptiometry. Measurements of muscle strength were obtained at baseline and every 3 months for 3 years. Maximal oxygen uptake was measured, and the level of physical activity was recorded. Compliance with the exercise program was excellent during the first year of the study, but decreased thereafter. At the end of 3 years, subject withdrawal was about 34% from the exercise group and about 22% from the control group (total subject withdrawal was about 30%). Muscle strength in the exercise group increased significantly at all involved skeletal sites (p values all < 0.001). There was a modest positive correlation between the BMD of Ward's triangle with spinal flexor strength (r = 0.32, p = 0.008) and with grip strength (r = 0.38, p = 0.001). Comparing study groups, we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group (our control group) on BMD at the spine, hip, or midradius measurement sites. In active, but not athletic premenopausal women, additional moderate weight-lifting exercises showed no significant effect on BMD.

Adult↗
PubMed1995

Separation of urinary estrogens by micellar electrokinetic chromatography.

Urinary estrogen levels are important for monitoring the normal pregnancy process as well as for the diagnosis of reproductive diseases. 17 beta-Estradiol and estrone are maintained at very low concentrations in urine and, therefore, are difficult to determine using standard chromatography with UV detection. In the present study, we describe a potential method for the determination of urinary estrogens (estrone, estradiol and estriol) using a solid-phase extraction and rapid capillary electrophoretic (CE) separations. Micellar electrokinetic chromatographic (MEKC) analysis was optimized by evaluating the number of surfactants in a 5 mM borate-5 mM phosphate separation buffer, of which sodium cholate (75-90 mM) was found to be optimal. Changing the hydrophobic character of the separation buffer with organic additives had a significant effect on the resolution of the three estrogens and an internal standard (d-equilenin). The addition of an organic additive (20% acetonitrile) was found to be necessary for the resolution of all components of the mixture. Substitution with 20% methanol provided a similar separation with better resolution but at the cost of increased analysis time. Analysis of two extracted urine samples from 18-weeks and 21-weeks pregnant women showed that, with the present technology, CE can provide adequate resolution and superior speed, but the sensitivity limits attainable with the existing technology may limit its utility to the measurement of estriol and estrone.

Chromatography, Liquid↗
PubMed1995

Role of parathyroid hormone in mediating nocturnal and age-related increases in bone resorption.

PTH has been postulated to play a role in both nocturnal and age-related increases in bone resorption. We tested this hypothesis directly in 10 young (ages 24-35 yr) and 10 elderly (ages 71-78 yr) normal women by measuring the cross-linked N-telopeptide of type I collagen (NTx), a marker for bone collagen breakdown, in 4-h urine collections before and during suppression of PTH secretion by a 24-h iv infusion of calcium. Serum ionized calcium and PTH levels were also measured every 2 h before and during the infusion. In both groups of women, serum PTH levels and urinary NTx excretion followed a circadian pattern before calcium infusion (analysis of variance, P = 0.0001) with peaks in the afternoon and at night for PTH and at night for urinary NTx. During the calcium infusion, the nocturnal urinary NTx excretion peak persisted (P = 0.0001), despite elimination of both PTH peaks. Urinary 24-h NTx excretion (nanomoles per millimoles of creatinine) at baseline was higher in the elderly women (mean +/- SEM, 25.7 +/- 2.1) than in the young women (19.3 +/- 1.7) (P < 0.01), and the decrease during calcium infusion was greater (7.5 +/- 1.9 vs. 4.1 +/- 1.5, P < 0.05). Therefore, the increase in serum PTH levels with age is one of the major factors responsible for the age-related increase in bone resorption. PTH does not mediate the circadian pattern of bone resorption but does play a role in setting the absolute level of bone resorption at which this pattern occurs.

Adult↗
PubMed1995

Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause--a clinical research center study.

To assess the mechanism by which estrogen replacement therapy (ERT) enhances renal calcium conservation in perimenopausal women, we studied 18 normal women in early postmenopause before and after 6 months of ERT (cyclic treatment with transdermal estradiol at 100 micrograms/day and medroxyprogesterone acetate at 10 mg/day for the first 12 days of each cycle). The changes after ERT were: serum ionized calcium and ultrafiltrable calcium, no change; serum intact PTH, 38.2% increase (P < 0.0001); serum 1,25-dihydroxyvitamin D, 23.8% increase (P < 0.0001); urinary calcium excretion, 33.3% decrease (P < 0.001); and deoxypyridinoline (a marker for bone resorption), 19.5% decrease (P < 0.0001). Also, ERT increased tubular reabsorption of calcium (TRCa; 97.6% +/- 0.2% to 98.7% +/- 0.1%; P < 0.0001), and this increase correlated with that in serum PTH (r = 0.49; P < 0.05). After the infusion of human PTH-(1-34), the TRCa maximum was greater after ERT than at baseline (99.4% +/- 0.1% vs. 99.0% +/- 0.1%; P < 0.0001), resulting in decreased calcium excretion (0.9 +/- 0.20 vs. 1.43 +/- 0.20 mumol/dL glomerular filtrate; P < 0.001). Thus, in early postmenopause, the major mechanism of increased renal calcium conservation after ERT is an increase in TRCa due to an increase in serum PTH because of estrogen-induced inhibition of bone resorption. However, ERT also may directly increase the TRCa maximum in response to PTH.

Adult↗
PubMed1995

Aspirin idiosyncrasy in systemic mast cell disease: a new look at mediator release during aspirin desensitization.

OBJECTIVE: To report the clinical responses and mediator-release profiles of an aspirin-sensitive man with systemic mast cell disease during aspirin desensitization. MATERIAL AND METHODS: We quantified the release of six mediators during aspirin desensitization. RESULTS: Although aspirin was administered cautiously with an initial dose of 20 mg, successful aspirin desensitization necessitated complete monitoring and resuscitation capabilities of a medical intensive-care unit for 4.5 days because of frequent, severe anaphylactoid responses. To our knowledge, this is the first report of a pronounced increase in plasma levels of the vasodilator peptide calcitonin gene-related peptide during episodes of aspirin-induced hypotension. Increases in plasma levels of calcitonin and serum levels of tryptase paralleled those of calcitonin gene-related peptide, but plasma levels of calcitonin remained increased for up to 18 hours. Urinary excretion of histamine and 1-methyl-4-imidazoleacetic acid also showed precipitous, although delayed, increases. Excretion of the prostaglandin D2 metabolite 11 beta-prostaglandin F2 alpha followed a bimodal pattern during aspirin desensitization; after severe hypotensive responses, the maximal value was more than 490,000 pg/mL, but the level decreased to less than 100 pg/mL after therapeutic serum levels of salicylate were attained. CONCLUSION: These data suggest that the hypotensive responses to aspirin in some patients with systemic mast cell disease may result from the combined effects of several mediators.

Adult↗
PubMed1995

How to reduce the risk factors of osteoporosis in Asia.

Osteoporosis can be predicted to be a new burden to public health in Asia. Currently, the incidence of osteoporosis-related fractures is lower there than in most western communities. By the year 2050, however, 50% of the 6.3 million hip fractures which occur worldwide will be in Asians as a result of an aging population, a decrease in physical activity and westernization of lifestyles. The cost of treatment and cure of these patients will be enormous, a sufficient financial burden to consume current economic gain and cripple the future advancing development of Asian countries. Individual risk factors for osteoporosis have been identified by the extensive Mediterranean Osteoporosis Study (MEDOS). Fortunately, Asians, the rural population and farmers in particular, have the favorable lifestyle identified by the study, including high physical activity and exposure to sunlight. Strikingly, tea drinking, a daily habit in Asia, is also identified as a protective factor against osteoporosis. In addition, bioflavonoids and phytoestrogen-rich soybeans and vegetables are consumed in large quantities by Asians. A soy diet reduces mortality in breast and prostate cancer because it contains weak estrogens. The weakly estrogenic phytoestrogens require further study to demonstrate their pharmacological effect in reducing the rate of osteoporosis. Public health education, however, is needed to encourage the Asian population to maintain their traditionally good lifestyle and to reduce the risk factors for osteoporosis. In turn, these steps may reduce the public health burden by 2050.

Estrogens, Non-Steroidal↗
PubMed1994

Regulation of insulin-like growth factors by antiestrogen.

Insulin-like growth factors are potent mitogens for breast cancer cell proliferation. This effect is modulated by the circulatory and extracellular IGFBPs as well as by the affinity of ligand binding receptors on the target cells. Antiestrogens have been shown to reduce both circulatory and microenvironmental IGF levels and thus suppress the IGF-I-induced growth of both ER-positive and ER-negative breast cancer cells. However, the effects of antiestrogens in down regulation of type I IGF receptor and in altering the autophosphorylation tyrosine kinase activity of EGF receptors are mainly observed in ER-positive cells. Furthermore, alteration of IGFBP by antiestrogens such as a marked increase of IGFBP-I production have been shown to inhibit the proliferative effect of IGF-I on ER-positive, but stimulate this effect, on ER-negative cells. Such differential effects from IGF receptor and IGFBP may explain the clinical outcome that tumor regression from antiestrogens is mainly observed in ER-positive type. This assumption based on IGF regulation alone is certainly an oversimplistic view amid the complexity of autocrine, paracrine, and endocrine functions.

Breast Neoplasms↗
PubMed1994

Intraoperative monitoring of parathyroid procedures by a 15-minute parathyroid hormone immunochemiluminometric assay.

OBJECTIVE: To report the recent development and validation of a sensitive 15-minute immunochemiluminometric assay (ICMA) of parathyroid hormone (PTH). DESIGN: The characteristics and applications of a new "rapid" PTH ICMA are described, and the advantages in comparison with other assays are discussed. MATERIAL AND METHODS: The 15-minute PTH ICMA was achieved by using a higher incubation temperature (45 degrees C rather than room temperature) and a concentration of tracer antibodies that was 5 times that in the regular 18-hour assay. The sensitivity, recovery, and linearity of dilution of the rapid ICMA were assessed, as was its ability to reflect intraoperative changes in PTH concentration after parathyroidectomy in patients with hyperparathyroidism. RESULTS: The sensitivity of the ICMA was 0.3 pmol/L in comparison with 0.08 pmol/L for the regular 18-hour assay (normal range, 1.0 to 5.0). The recovery of added PTH was 84% by using ethylene-diaminetetraacetic acid-plasma as the specimen. Moreover, the linearity of specimens after dilution was good. The assay demonstrated a rapid response to parathyroid gland removal. In most patients, PTH levels declined precipitously (to less than 30% of basal values) within 5 minutes after parathyroid resection. PTH levels remained low to undetectable at 10 and 20 minutes after excision. CONCLUSION: This rapid PTH ICMA may be of assistance to endocrine surgeons in the monitoring of PTH function after both parathyroid and thyroid surgical procedures.

Humans↗
PubMed1994

Endothelin in human congestive heart failure.

BACKGROUND: Although recent investigations report the elevation of plasma endothelin (ET) in congestive heart failure (CHF), it remains unclear if this elevation is that of the biologically active peptide ET-1 or of its precursor big-ET. Furthermore, it is unclear if such elevation is associated with increased myocardial ET and if the molecular form from cardiac tissue is altered ET. Last, it remains to be established whether circulating ET is increased at the earliest stage of CHF in patients with asymptomatic left ventricular dysfunction and correlates with the magnitude of ventricular dysfunction. METHODS AND RESULTS: The present study was designed to investigate concentrations and molecular forms of ET in plasma and cardiac tissue in healthy subjects and CHF patients with New York Heart Association (NYHA) class I through IV using cardiac radionuclide angiogram, cardiac myocardial biopsy, radioimmunoassay, gel permeation chromatography (GPC), and immunohistochemical staining (IHCS). Plasma ET was increased only in patients with moderate (NYHA class III) or severe (NYHA class IV) CHF compared with healthy subjects and individuals with asymptomatic (NYHA class I) or mild (NYHA class II) CHF. The elevation of circulating ET in CHF showed a negative correlation with left ventricular ejection fraction and cardiac index and a positive correlation with functional class and left ventricular end-diastolic volume index. GPC demonstrated that immunoreactive plasma ET was ET-1 in healthy subjects and both mature ET-1 and its precursor big-ET in severe CHF patients, with big-ET the predominant molecular form. Cardiac tissue concentrations and IHCS revealed ET presence in healthy atrial and ventricular tissue, which were not different in severe CHF. GPC revealed that the molecular form of cardiac ET was ET-1 in both healthy and CHF hearts. CONCLUSIONS: The present study establishes for the first time that the elevation of plasma ET in severe human CHF represents principally elevation of big-ET. Second, ET is present in healthy and failing myocardia, and its activity by both immunohistochemistry and radioimmunoassay is not changed in CHF. Furthermore, the elevated plasma ET is characteristic of severe CHF and not asymptomatic or mild CHF. In addition, the degree of plasma elevation of ET correlates with the magnitude of alterations in cardiac hemodynamics and functional class. The present study confirms and extends previous investigations of ET in human CHF and establishes the evolution of circulating and local cardiac ET in the spectrum of human CHF.

Chromatography, Gel↗
PubMed1994

Insulin-like growth factor-I comparisons in healthy twin children.

Insulin-like growth factor-I (IGF-I) levels in plasma were measured in healthy twin children. The within-pair correlation for 43 monozygotic pairs was r = 0.91 (P < or = 0.0001), an association significantly higher than that for same sex dizygotic pairs (r = 0.40; P < or = 0.06). The high correlation for monozygotic twins indicated a marked genetic influence on IGF-I levels. After correction for age and sex, the correlation between IGF-I level and height was r = 0.38 (P < or = 0.0001). These findings provide clear evidence that IGF-I levels correlate with height, a growth characteristic known to be genetically controlled.

Aging↗
PubMed1994

Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma.

We used a newly developed immunochemiluminometric assay of proinsulin to determine its relative utility vis-à-vis C-peptide and insulin for the diagnosis of insulinoma. The evaluation was conducted in 20 consecutive patients with histologically confirmed insulinoma and 22 normal subjects who underwent a prolonged fast according to a standard protocol. Patients with insulinoma fasted to the point of demonstrating Whipple's triad; normal subjects fasted to 72 h. At the end of the prolonged fast, when the glucose value was 2.8 mmol/L or less (50 mg/dL), all three hormones had equal sensitivity (100%) in detecting insulinoma with no overlap with the values of normal subjects. When glucose levels were between 2.8 mmol/L (50 mg/dL) and 3.3 mmol/L (60 mg/dL) at the end of the prolonged fast, proinsulin was better than C-peptide and insulin in the diagnosis of insulinoma. The sensitivity was 90% for proinsulin and 85% for both C-peptide and insulin. Therefore, proinsulin not only is useful for the diagnosis of insulinoma, but it may have greater diagnostic accuracy than C-peptide and insulin.

Animals↗
PubMed1994

Abnormalities of parathyroid hormone secretion in elderly women that are reversible by short term therapy with 1,25-dihydroxyvitamin D3.

Serum PTH concentrations increase with aging and may play an important causal role in age-related bone loss. To better define possible PTH secretory abnormalities with aging, we studied 10 young (aged 27-34 yr) and 10 elderly (aged 71-77 yr) women using sequential infusions of calcium and EDTA. To assess possible age-related resistance of PTH secretion to modulation by 1,25-dihydroxyvitamin D [1,25-(OH)2D], the infusions were repeated after 1 week of oral 1,25-(OH)2D3 therapy (1 microgram/day). Baseline serum intact PTH concentrations were higher in the elderly compared to the young women (mean +/- SEM, 3.8 +/- 0.5 vs. 2.7 +/- 0.4 pmol/L; P = 0.03). In addition, the elderly women had a significantly higher maximal PTH response to hypocalcemia compared to the young women (16.6 +/- 1.1 vs. 12.8 +/- 1.0 pmol/L; P = 0.03). The elderly women also had a greater nonsuppressible component of PTH secretion (0.8 +/- 0.1 vs. 0.4 +/- 0.1 pmol/L; P < 0.001). The set-point for PTH secretion, however, was identical in the elderly and young women (1.18 +/- 0.01 vs. 1.19 +/- 0.01 mmol/L; P = NS). After 1,25-(OH)2D3 administration, both groups had similar reductions in baseline and maximally stimulated PTH levels, indicating that elderly women have normal responsiveness to 1,25-(OH)2D3 suppression of PTH secretion. In addition, maximally stimulated PTH levels in the 1,25-(OH)2D3-treated elderly women decreased to the pretreatment values of young women (13.3 +/- 1.1 vs. 12.8 +/- 1.0 pmol/L; P = NS). thus, elderly women have greater basal, maximal, and nonsuppressible levels of PTH secretion, without alterations in the set-point. These abnormalities are similar to those found in patients with secondary hyperparathyroidism and parathyroid hyperplasia. Further, the abnormal PTH secretory dynamics in elderly women are reversible by short term 1,25-(OH)2D3 therapy.

Adult↗
PubMed1993

Clinical performance of an extraction calcitonin radioimmunoassay.

An extraction radioimmunoassay of calcitonin (CT) was used to replace the direct radioimmunoassay, in which false-negative results (normal basal CT values but above normal ["positive"] results after pentagastrin stimulation) occurred in 26 to 30% of cases. During the past 6 years, 170 pentagastrin stimulation tests were performed in 135 patients at our institution. We reviewed the results to determine whether extraction radioimmunoassay yielded improvement. Of the 135 patients, 6 (4.4%) had indeterminate results of pentagastrin stimulation tests that consisted of normal basal levels but increased values after pentagastrin stimulation, a considerable improvement over the results with direct assay. Six other patients had indeterminate results of pentagastrin testing--increased basal CT levels but normal values after pentagastrin stimulation. Indeterminate results of pentagastrin tests occurred primarily in postoperative or preoperative patients with a family history of medullary thyroid carcinoma (MTC). The reasons for the indeterminate results were unclear, as was their importance as a prelude to disease, but two preoperative patients with indeterminate results eventually had positive results and were found to have MTC at operation. We conclude that extraction radioimmunoassay is more reliable than direct radioimmunoassay for the diagnosis of MTC. Determination of a basal CT value and of the CT value after pentagastrin stimulation is sufficient for diagnosing MTC.

Adult↗
PubMed1993

Efficacy of vitamin D3 derivatives in the treatment of psoriasis vulgaris: a preliminary report.

The efficacy of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the new analogue calcipotriene (MC 903) in the treatment of psoriasis was investigated. Eight patients with psoriasis were enrolled in a pilot study with systemically administered vitamin D3 and were given 1,25(OH)2D3 (Rocaltrol; Hoffmann-La Roche) in dosages from 0.5 microgram to 2 micrograms/day for a 6-month trial. In one patient, the psoriatic plaques resolved within 2 months after treatment (0.5 microgram/day) was initiated. Moderate improvement was noted in one other patient (1 microgram/day). The serum level of 1,25(OH)2D before treatment was not less than the normal range of the adult population. Side effects of systemically administered 1,25(OH)2D3 included a dose-dependent increase in the 24-hour urinary calcium excretion and a decrease in the total number of platelets. Seven patients with symmetric plaque-type psoriasis were treated topically with 2 micrograms/g of 1,25(OH)2D3 in petrolatum. During 3 months of follow-up, mild improvement was noted in three patients. Five patients in the calcipotriene study were part of a nationwide double-blind placebo-controlled trial by Bristol-Myers Squibb. Moderate to marked improvement was noted in the two patients who received 50 micrograms/g of calcipotriene topically. The three patients who received placebo showed no response. We conclude that a subset of patients with psoriasis responds well to 1,25(OH)2D3. Calcipotriene is efficacious and an excellent alternative to topically applied corticosteroids.

Administration, Oral↗