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Biomedical subjects

J Nieves

Publications and source records attributed to J Nieves.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bone structure in postmenopausal hyperparathyroid, osteoporotic, and normal women.

The purpose of this study was to test the hypothesis that patients with mild primary hyperparathyroidism are protected against postmenopausal (PM) loss of cancellous bone architecture. To achieve this, we compared bone structure and turnover in iliac bone biopsies from three groups: 16 women with mild primary hyperparathyroidism (PHPT; 58.2 +/- 2.2 years, 11.5 +/- 1.7 years PM), 17 women with untreated primary osteoporosis (OP; 65.1 +/- 2.0 years, 17.2 +/- 2.3 years PM), and 31 healthy women (N; 59.8 +/- 1.4 years, 13.4 +/- 1.5 years PM). The bone formation rate was significantly higher in PHPT than in either OP or N, and not different between OP and N. Cancellous bone volume, total strut length, and indices of connectivity (node number, node to node strut length, and node to terminus ratio) were significantly lower in OP than in either PHPT or N but were the same or higher in PHPT than in N. Indices of disconnectivity were significantly lower in PHPT than in N, whereas they were the same or higher in OP than N. The data were also analyzed in subgroups matched by years PM with no changes in the results. These findings indicate that osteoporotic patients with normal bone turnover have low bone volume and microarchitectural deterioration, while patients with mild PHPT have normal bone volume and normal or greater trabecular connectivity despite higher bone turnover. These findings suggest that mild PHPT protects against the loss of cancellous bone structure that normally follows menopause.

Bone and Bones↗
PubMed1995

Postmenopausal osteoporosis: patient choices and outcomes.

OBJECTIVE: Only two medications, estrogen and injectable salmon calcitonin, are currently approved by the FDA for the treatment of osteoporosis. Oral etidronate has been investigated but not approved for osteoporosis therapy. We compared the three available anti-resorptive medications in untreated osteoporotic women. DESIGN: A nonrandomized, open label trial. After baseline biochemistry and bone mineral density (BMD) determinations, subjects self-selected therapy based on descriptions of the three drugs which were similar for all patients. Bone densitometry of the lumbar spine, femoral neck and distal and proximal forearm sites was repeated every 6 months. RESULTS: Twenty-one patients chose estrogen, 20 chose etidronate and 11 chose calcitonin. Fear of breast cancer was the most common reason given for not choosing estrogen therapy. Mean age was slightly lower and spine and hip bone densities slightly higher in the estrogen group compared with both the etidronate and calcitonin groups. In the lumbar spine, all three agents resulted in similar small increments (mean increments 1.2-4.4% at 2 years). In the estrogen group, there was no change in femoral neck density while there were significant losses in both calcitonin and etidronate groups (3.1-4.9%). In the forearm, there was either no change (distal site) or an increment (proximal site) in the estrogen group, while both etidronate and calcitonin groups demonstrated a mean loss at both sites over the 2-year observation period. CONCLUSIONS: These preliminary results suggest that all three agents appear equally effective at maintaining or increasing BMD of the lumbar spine, while estrogen appeared more effective at maintaining or increasing BMD of the appendicular skeleton. This study underscores the need for an alternative to estrogen therapy which is equally effective and can be given orally for those in whom estrogen is either contraindicated or undesirable.

Aged↗
PubMed1994

Milk and bones.

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Animals↗
PubMed1994

High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton.

The effects of acute pharmacologic steroid treatment on skeletal and mineral metabolism were assessed in 56 multiple sclerosis patients who were to receive 1 g intravenous methylprednisolone for 10 days, followed by a 4 day intravenous and 28 day oral glucocorticoid taper. Serum and urine samples were obtained at baseline and then within 3 days, 1, 2, and 3 weeks after beginning steroids. A subset of patients (n = 11) had sampling throughout the 6 weeks of steroid administration and up to 8 weeks afterward. All mean basal biochemistries were normal except 25(OH)D, which was in the "insufficient" range (25-50 nM) at 10 nM. During and after steroid administration, there were no changes in ionized calcium, 25(OH)D, urinary hydroxyproline, or pyridinoline. There was an increase in 1,25(OH)2D and a decrease in serum phosphorus, accompanied by an increase in urinary phosphate clearance, within 3 days of administration (p < 0.006). Serum osteocalcin (BGP) decreased to below assay sensitivity limits within 3 days of steroid administration (p < 0.0002), increasing thereafter but remaining at 50% of baseline by the third week. PTH(1-84) increased to a peak at week 2 (p < 0.02), after both the 1,25(OH)2D peak and the serum phosphorus nadir. Tartrate-resistant acid phosphatase, urinary calcium, and urinary cyclic AMP all increased above baseline (p < 0.05) with a pattern similar to that of PTH. To investigate further the immediate effects of steroid administration, serum samples were obtained at the same four times on both the day before and the day after the first intravenous methylprednisolone dose in a randomly chosen subset of patients (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Effects of estrogen on response to edetic acid infusion in postmenopausal osteoporotic women.

We and others have hypothesized that estrogen helps preserve bone mass by affecting the PTH/vitamin D regulation of skeletal metabolism. To evaluate this theory, we tested the effect of estrogen administration on parathyroid sensitivity to hypocalcemic challenge. Subjects were postmenopausal osteoporotic women recruited from a tertiary care clinic (9 untreated and 12 receiving hormone replacement therapy at the time of the investigation). After baseline serum and urine testing, edetic acid (50 mg/kg) was infused over a 2-h period. Serum and urine samples were obtained over 5 h and 24 h after beginning the infusion. Serum ionized calcium dropped equally in both groups of women. There were overall group differences in PTH-(1-84) secretion (P < 0.02), with a greater peak (P < 0.04) and a longer period of elevation (P < 0.01) in the untreated than in the hormone-treated osteoporotic women. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] and phosphorus as well as urinary phosphate and cAMP responded similarly in the two groups of women. Estrogenized osteoporotic women demonstrate a smaller PTH increment to hypocalcemia, indicating that the parathyroid has reduced sensitivity under the influence of estrogen. Despite the smaller PTH increase in estrogenized individuals, renal responses to PTH were the same as those in untreated osteoporotic women, implying an estrogen-mediated increase in the sensitivity of the kidney to PTH.

Administration, Oral↗
PubMed1994

High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis.

BACKGROUND: Female patients with multiple sclerosis (MS) are at risk for osteoporosis because of gender, immobility, and corticosteroid use. METHODS: Bone mineral density (BMD) was measured by dual x-ray absorptiometry in 80 female MS patients admitted to a tertiary care hospital. All patients completed a questionnaire that included measurements of dietary intake and sunlight exposure. Biochemical indices of bone metabolism and turnover were measured in a random sample of 52 patients. RESULTS: BMD of the lumbar spine and femoral neck was 1 to 2 SDs lower in MS women compared with a healthy reference population. BMD was lower in patients with more severe MS. The mean 25(OH)D level of the sample population (43 nmol/l) was in the insufficient range, and 12 patients (23%) had frank vitamin D deficiency (< 25 nmol/l). BMD and age-related BMD (z scores) at all skeletal sites measured were lowest when 25(OH)D levels were deficient. Parathyroid hormone (PTH) was frankly elevated in 13% of patients. PTH levels were negatively correlated with 25(OH)D levels and with BMD. Dietary intake of vitamin D was below the recommended level in 80% of patients, and 40% reported no weekly sunlight exposure. After controlling for age, cumulative steroid use was not a determinant of BMD. CONCLUSIONS: BMD was significantly reduced in female MS patients, which might increase fracture risk two- to threefold. Vitamin D deficiency with secondary hyperparathyroidism is prevalent and is probably a significant cause of low BMD in this population. Vitamin D deficiency in the female MS patient might be safely and inexpensively corrected by the routine use of vitamin D supplements.

Adult↗
PubMed1993

Calcium homeostasis of an elderly population upon admission to a nursing home.

OBJECTIVE: To evaluate the skeletal health, calcium, and vitamin D homeostasis of patients upon their entry to a long-term-care facility. Factors that could contribute to the risk of future osteoporotic fractures were also evaluated. DESIGN: Cross-sectional study. PATIENTS: Two hundred eighty-seven consecutive admissions were invited to participate; 109 patients were recruited into the study. MEASUREMENTS: A high prevalence of low to low-normal circulating levels of 25(OH)D was found in nursing home residents upon their admission to the nursing home, with 86% of the patients having circulating 25(OH)D levels of less than 50 nmol/L and 41% having levels below 25 nmol/L. Frankly elevated parathyroid hormone levels were found in 16% of the patients. Additionally, alkaline phosphatase and osteocalcin levels were elevated in 23% and 13% of the patients, respectively. Bone mineral measurements were in the osteoporotic range for 85% of the nursing home residents. Bone density results for females with a history of any classic osteoporotic fracture were significantly lower than for those with no fracture history (68.5 arbitrary units (AU) for those with no fracture history, 58.8 AU in those with history of hip fracture; P < 0.05). The bone mineral measurements were higher in women with adequate 25(OH)D compared with women with deficient or borderline 25(OH)D with and without fracture history. Levels of 25(OH)D were positively correlated with urine calcium/creatinine (r = .24; P = 0.03) and 1,25(OH)2D (r = .28; P = 0.01) and were negatively correlated with 1-84 PTH (r = -.24; P = 0.02). CONCLUSION: Hypovitaminosis D is prevalent among elderly patients entering a nursing home with secondary hyperparathyroidism and apparently increased bone turnover present in patients with circulating 25(OH)D levels below 50 nmol/L. Bone density measurements showed that a majority of the individuals entering a nursing home are osteoporotic. There is a positive association between 25(OH)D levels and bone mass and a negative association between 25(OH)D levels and a history of fracture.

Activities of Daily Living↗
PubMed1993

Subcutaneous administration of the amino-terminal fragment of human parathyroid hormone-(1-34): kinetics and biochemical response in estrogenized osteoporotic patients.

A standard dose (400 U or 25 micrograms) of human (h) PTH-(1-34) was administered sc in 11 estrogen-treated patients with postmenopausal osteoporosis. Increments in circulating hPTH-(1-34) were brisk, peaking at 30 min, with variable peak levels averaging 10 times normal. Clearance of the peptide from the circulation followed an expontential pattern, with a mean t1/2 of 75 min. Peptide administration was followed by an immediate decline in serum concentrations of PTH-(1-84), which remained suppressed at about 65% of the basal value for the duration of the study (4 h). Serum calcium did not increase until 120 min, thus occurring after the diminution in PTH-(1-84). Serum phosphorus declined promptly as urinary phosphate excretion increased. There were no clear changes in urinary calcium excretion, but urinary cAMP excretion increased within 120 min. In 9 of 11 patients, the serum concentration of 1,25-dihydroxyvitamin D increased, with mean levels increasing progressively after 90 min to approximately 30% above baseline (P < 0.05). In conclusion, sc administration of 25 micrograms hPTH-(1-34) produces significant short term changes in mineral homeostasis that appear to be mediated by the kidney, parathyroid gland, and skeleton, with the latter displaying the most delayed response.

Calcitriol↗
PubMed1993

Effect of blood-brain barrier and blood-tumor barrier modification on central nervous system liposomal uptake.

In this study of 25 central nervous system (CNS) tumor-bearing rats, the CNS biodistribution of intravenously administered, indium-labeled liposomes was investigated. In 16 animals, the blood-brain barrier and blood-tumor barrier were modified using intracarotid administration of etoposide. In control animals, analysis by autoradiography and well-counting experiments demonstrated uptake of liposomes in the tumor-bearing hemisphere (% injected dose/g tissue = 0.135) with minimal uptake in the non-tumor-bearing hemisphere (% injected dose/g tissue = 0.007), p < 0.01. Unilateral intracarotid etoposide administration enhanced liposome uptake in both hemispheres-0.215 and 0.023 (tumor-bearing and nontumor-bearing), respectively. The presence of meningeal tumor involvement in nontumor-implanted hemispheres increased liposomal uptake 10-fold. These findings may have clinical applicability in designing therapeutic protocols for the treatment of CNS tumors.

Animals↗
PubMed1993

Bone mass among premenopausal women.

Bone mass in early adult life, or peak bone mass, is primarily under genetic control, although recent data suggest that alterations in nutrition and life style during growth may modify the genetic potential. Cross-sectional data indicated that upon completion of growth, there was a period of skeletal consolidation that resulted primarily from increased width of cortical bones. Data on cancellous bone are conflicting. Cross-sectional data suggest that cancellous bone mass reaches a maximum at about age 18 years. Bone mass in the spine appears stable until the beginning of menopause, unless there are other disturbances of ovarian function. On the basis of cross-sectional data, significant bone loss in the femoral neck in premenopausal women appears to occur prior to changes in ovarian function. This decline in hip density is also independent of body size, nutritional influences, or other variables thought to influence bone mass. Longitudinal data are not available to confirm the reduction in femoral neck bone mass. Preliminary data indicate that modest disruptions of ovarian function, insufficient to result in frank amenorrhea, might impact negatively on bone mass. A detailed longitudinal study of menstrual and other factors controlling bone mass in premenopausal women is needed. If bone mass can be modified, ensuring a maximal skeletal mass becomes a viable possibility for prevention of osteoporosis.

Adolescent↗
PubMed1992

EEG coherence as a predictor of spike propagation.

The relationship between resting EEG coherence and the propagation of spike activity from an experimental cortical focus was investigated in 6 rats. EEG was collected from an array of 6 epicortical electrodes positioned over the posterior hind limb sensorimotor (HL) and frontal (Fr1, Fr2) cortices. Coherence decreased non-linearly for all frequency bands with increasing interelectrode distance. The greatest decrement in coherence occurred in the region corresponding to the junction between hind limb (HL) and frontal (Fr1) cortices. The decrease in coherence was greatest for the highest frequency band for all interelectrode pairs. A spike focus was induced in all 6 animals following the application of bicuculline at the most posterior electrode of the cortical array. In 5 of the 6 animals spike propagation was delayed at the junction of HL and Fr1 cortices, where the greatest decrease in coherence was observed. In one animal spike activity never advanced across this region. These results demonstrate an association between intracortical coherence and the spatial propagation of spike activity. The function of short and long cortico-cortical pathways as mediators of both EEG coherence and cortical spike propagation are discussed.

Action Potentials↗
PubMed1992

The effect of graded spinal cord injury on the extrapyramidal and pyramidal motor evoked potentials of the rat.

This study investigated the differential effects of graded spinal cord injury on the rat extrapyramidal motor evoked potential (exp-MEP) and pyramidal motor evoked potential (pyr-MEP) and the prognostic value of these effects in predicting postinjury motor performance in the rat model. In 20 rats subjected to graded spinal injury (10-100 g-cm), there was a differential injury threshold for ablation of exp-MEP and pyr-MEP. All peaks of the pyr-MEP were extinguished in the animals subjected to impact forces of 50 g-cm and above (n = 12). In contrast, the exp-MEP was completely abolished in only two animals at injuries of 80 g-cm or above. A residual exp-MEP response persisted in the remaining 18 animals. Motor performance was monitored in 16 additional animals for up to 1 week after spinal injury. The pyr-MEP was abolished in 100% of the rats subjected to a 50-g cm injury (n = 7), whereas the exp-MEP persisted up to the highest impact forces (80 g-cm). Hind leg paralysis was present in the five rats where the pyr-MEP was extinguished but with persistence of the exp-MEP. An 80% reduction in the amplitude of the pyr-MEP in four animals resulted in mild ataxia with motor improvement at the end of a week. An increase or a 70% loss in pyr-MEP peak amplitude resulted in no clinical motor deficits (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗