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Biomedical subjects

J C Gallagher

Publications and source records attributed to J C Gallagher.

At least 73 records · Page 4Linked to original sources

Endometrial histology and bleeding patterns in menopausal women treated with estrogen and continuous or cyclic progestin.

Thirty-six postmenopausal women were randomized to three groups in a double-blind, prospective study. All were treated for three months with conjugated estrogens (Premarin), 0.625 mg daily, and three different doses of a progestin (Provera), 2.5 mg daily, 5 mg daily or 5 mg during the last 12 days of a 28-day cycle. We found that the endometrium was maintained in an inactive phase in 100% of the women given continuous daily progestin but in only 25% of those given cyclic progestin. Bleeding occurred in 100% of subjects given cyclic progestin and in 50% of those given continuous progestin; however, bleeding episodes diminished with time in those on continuous progestin. A hormonal regimen that leads to reduced or absent bleeding and an inactive endometrium is preferable for postmenopausal women if estrogen therapy is to be used for the long term after menopause.

Antineoplastic Agents↗

Vertebral morphometry: normative data.

Morphometric measurements of the thoracic and lumbar vertebrae were carried out on spinal radiographs of 150 normal women. A normal range was established for each individual vertebra. There was no change in the anterior height of the thoracic or lumbar vertebrae with age but there was a small significant decrease in the posterior height of the lumbar vertebrae with age. This is unlike the pattern seen in osteoporotics in whom a decrease in anterior height of the vertebrae is the first clinical manifestation of spinal osteoporosis. At the present time diagnosis of an osteoporotic spinal fracture is usually based on a subjective decision. Normative data for the vertebral dimensions should help improve the accuracy of diagnosis.

Adult↗

Total bone calcium in normal women: effect of age and menopause status.

Bone density in different regions of the skeleton was measured in 392 normal women aged 20-80 years by dual photon absorpiometry. In premenopausal women, aged 25-50 years, multiple regression analysis of regional bone density on age, height, and weight showed a small significant decrease in total bone density (less than 0.01) but no significant change in other regions of the skeleton. In postmenopausal women there were highly significant decreases in all regions of the skeleton (p less than 0.001), and bone density in these areas decreased as a logarithmic function of years since menopause. Based on multiple regression analyses, the decrease in spine density and total bone calcium was 2.5-3.0 times greater in the 25 years after menopause than the 25 years before menopause. The largest change, however, occurred in the first five years after menopause. During this time the estimated annual change in spine density and total bone calcium was about 10 times greater than that in the premenopausal period. These results demonstrate the important effect of the menopause in determining bone mass in later life.

Adult↗

Ovarian pregnancy: a series of 24 cases.

This study was undertaken to investigate 24 cases of ovarian pregnancy identified by retrospective analysis of 148,734 deliveries at 6 hospitals between 1952 and 1980, and to review pertinent literature. Although ovarian pregnancy is rare, it was shown to occur 4 times more frequently than previously believed--on the order of 1 per 7000 deliveries and slightly less than 3% of all ectopic pregnancies. Awareness of the possibility of ovarian pregnancy and closer histologic examination of surgical specimens are critical factors for increased recognition. The use of intrauterine contraceptive devices was not associated with an absolute increase in occurrence of ovarian pregnancy. More than half the cases involved a history of previous reproductive system pathology or infertility. Clinical presentations of ovarian and tubal pregnancies are similar and differentiation can be made only after microscopic examination of tissue specimens. Even then, diagnosis of primary ovarian pregnancy may be elusive due to increasing tissue destruction and greater use of conservative surgical procedures. When the organized diagnostic approach should be followed. Culdocentesis should be performed whenever hemoperitoneum is suspected. The preferred therapeutic procedure is ovarian cystectomy or ovarian wedge resection. No maternal mortality occurred in any of the cases reviewed. An extremely rare case of ovarian pregnancy following vaginal hysterectomy is presented.

Adolescent↗

1,25-Dihydroxyvitamin D3: short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis.

We evaluated the effects of therapy with a small dose (0.5 microgram/day) of 1,25-dihydroxyvitamin D3 in 12 previously untreated patients with postmenopausal osteoporosis. Combined radiocalcium kinetic and balance studies showed that at base line, net calcium absorption (mean +/- SEM) was low (7 +/- 3%), calcium balance was negative (-59 +/- 22 mg/day), and bone resorption rate (297 +/- 40 mg/day) exceeded bone formation rate (239 +/- 36 mg/day). After short-term therapy (6-8 months), calcium absorption was normal (27 +/- 3%, P less than 0.001 for difference from base line), calcium balance had improved (+2 +/- 26 mg/day, P less than 0.05), and bone resorption rate (195 +/- 35 mg/day, P less than 0.01) had decreased more than bone formation rate (197 +/- 26 mg/day, NS). Compared with base-line values, after long-term therapy (2 years) the increased level of calcium absorption was maintained (27 +/- 3%, P less than 0.001), but calcium retention declined to a level intermediate (-27 +/- 24 mg/day, NS) between base-line and short-term treatment values, and both bone resorption rate (294 +/- 33 mg/day, NS) and bone formation rate (267 +/- 34 mg/day, NS) increased. Urinary hydroxyproline excretion was lower than before treatment (26.3 +/-2.0 mg/day) after both short-term (21.1 +/- 1.6 mg/day, P less than 0.001) and long-term (22.0 +/- 1.8 mg/day, P less than 0.01) treatments. Trabecular bone volume was 11.3 +/- 1.0% at base line and increased to 16.0 +/- 1.2% (P less than 0.01) after long-term treatment. By contrast, the eight patients studied before and after 6-8 months of placebo treatment had no significant change in any variable.

Bone and Bones↗

Vitamin D and bone health in the elderly.

The state of vitamin D nutrition depends on synthesis in the skin under the influence of sunlight as well as on dietary intake. In European countries that do not fortify milk with vitamin D, reduced sun exposure is the major factor leading to a fall in body stores of vitamin D with age and to a high frequency of hypovitaminosis D in the elderly sick. In the US, because vitamin D is added to milk and the use of vitamin D supplements is more common, the dietary intake of vitamin D is relatively more important than in Europe, and the total vitamin D intake and body stores of vitamin D are generally higher. Nevertheless, body stores of vitamin D probably fall with age in the US as they do in Europe, and it is likely that some sick elderly persons in the US, especially among those confined to institutions, become vitamin D deficient. For several reasons, the vitamin D requirement increases with age, and a total supply of 15 to 20 micrograms/day (600 to 800 IU) from all sources is recommended. Special attention should be paid to persons most likely to need supplementation, such as the housebound, persons with malabsorption, and persons with interruption of the enterohepatic circulation. Osteomalacia, the bone disease produced by severe vitamin D deficiency, is less common in the US than in Europe, but subclinical vitamin D deficiency may contribute to the pathogenesis of hip fractures, both through increased liability to fall and through PTH-mediated bone loss. The extent to which vitamin D deficiency contributes to hip fractures in the US is unknown, and is an important area for future research. Excess intake of vitamin D or of its metabolites may result in hypercalcemia and extra-osseous calcification, particularly in arterial walls and in the kidney, leading to chronic renal failure. The dose of vitamin D that causes significant hypercalcemia is highly variable between individuals but is rarely less than 1000 micrograms/day. Smaller doses can cause hypercalciuria and nephrolithiasis and possibly impaired renal function. Vitamin D administration may raise plasma cholesterol but there is no convincing evidence that the risk of myocardial infarction is increased. The recommended total supply for the elderly of 20 micrograms/day is most unlikely to be harmful, except in patients with sarcoidosis or renal calculi.

Adult↗

Calcium nutrition and bone health in the elderly.

The average elderly person is in negative calcium balance and accordingly is losing bone mass. While factors such as decreased mechanical loading of the skeleton undoubtedly figure in this age-related loss, a growing body of evidence suggests that inadequate calcium intake may contribute to this loss. On any given day men and women in the US 65 yr or older ingest about 600 and 480 mg calcium, respectively. Calcium intake in the elderly is less than in the young, and reduced absorption efficiency further lowers effective intake. Additionally, other nutrients such as protein and fiber, taken in excess, effectively increase the calcium requirement. Estrogen withdrawal at menopause leads to a decrease in intestinal calcium absorption efficiency and in renal calcium conservation, both effects equivalent to an effective increase in calcium intake requirement. Thus it is not surprising that all studies of mean requirements for zero balance performed in elderly subjects have yielded values above the current RDA for the US. The available evidence thus suggests that the RDA for adults should surely not be lowered below its current level (800 mg), but that, instead, it ought to be raised. It is not possible to say with certainty to exactly what level, but available evidence is compatible with allowances of at least 1200 to 1500 mg/day. Further, the evidence indicates that the mean requirement ought to be thought of as a complex function of age, sex, absorption efficiency, intake of protein, fiber, and probably other nutrients, estrogen status, and mechanical loading. Extensive experience with calcium supplements indicates that daily intakes up to at least 2.5 g of elemental calcium are quite safe in all persons except for certain subsets of the population uncommon among the elderly (eg, those with sarcoidosis, active tuberculosis, or other absorptive hypercalciuric syndromes). At the same time it must be said that osteoporosis is a complex, multifactorial disorder, and that factors unrelated to calcium nutrition undoubtedly play important, even dominant roles in many--perhaps most--osteoporotics. The available evidence, taken together, does not indicate that raising calcium intake will abolish the problem of osteoporosis. It does indicate, however, that calcium nutrition is considerably more important in the genesis of osteoporosis than has been commonly thought for the past 35 yr. As our listing of "important issues" indicates, the full extent of that importance, in both pathogenesis and prophylaxis, remains to be elucidated.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis.

Osteoporotic women have decreased calcium absorption and decreased serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] and are usually in negative calcium balance. Estrogen therapy improves calcium balance in patients with postmenopausal osteoporosis. In birds, estrogen administration increases the conversion of 25-hydroxyvitamin D (25OHD) to 1,25-(OH)2D. To determine if estrogen therapy affects vitamin D metabolism in human subjects, we studied 21 osteoporotic women before and after 6 months of treatment. We compared groups treated with either placebo (9 patients) or conjugated equine estrogen (1.2-2.5 mg/day; 12 patients). Fractional calcium absorption (mean +/- SE) was unchanged after treatment with placebo (0.51 +/- 0.03 to 0.52 +/- 0.01) but increased after treatment with estrogen (0.53 +/- 0.02 to 0.65 +/- 0.04; P < 0.005). The increase after estrogen was similar to the increase observed in 10 additional osteoporotic women treated for 6 months with a small dose of 0.5 microgram/day 1,25-(OH)2D (0.54 +/- 0.03 to 0.68 +/- 0.04; P < 0.005). Serum 1,25-(OH)2D was unchanged after treatment with placebo (27.5 +/- 1.3 to 27.6 +/- 1.7 pg/ml) but increased after treatment with estrogen (23.6 +/- 2.7 to 33.2 +/- 3.7 pg/ml; P < 0.005). Serum immunoreactive parathyroid hormone (PTH) increased (23.0 +/- 4.2 to 32.7 +/- 4.6 microliter eq/ml; P < 0.05) after estrogen but not after placebo treatment. After treatment with estrogen, the increases in serum immunoreactive PTH and serum 1,25-(OH)2D were correlated (r = 0.68; P < 0.05), and the increases in serum 1,25-(OH)2D and calcium absorption were highly correlated (r = 0.89; P < 0.001). We conclude that estrogen treatment increases calcium absorption in postmenopausal osteoporosis by increasing serum 1,25(OH)2D. This effect appears to be mediated indirectly through stimulation of renal 1 alpha-hydroxylase by increased serum PTH.

Aged↗

The effect of age on serum immunoreactive parathyroid hormone in normal and osteoporotic women.

Serum iPTH was measured in a large series of normal and osteoporotic women as a function of age, with radioimmunoassays using three antisera: GP-1M, which recognizes primarily a region within the 44--68 amino acid sequence of PTH; CH-12M, which appears to recognize primarily intact hormone; and CH-14M, which recognizes primarily a region within the 1--34 amino acid sequence of PTH. In normal women 20 to 90 years of age, serum iPTH increased significantly with age (p less than 0.001); the proportional increase was greater when measured with antiserum GP-1M (80%) than when measured with antiserum CH-12M (30%), which suggests that the increase in circulating carboxyl fragments of PTH was greater than the increase in circulating intact PTH. In 40 patients with postmenopausal osteoporosis, the mean value for serum iPTH assayed by antiserum GP-1M did not differ significantly from that for age-matched normal women; however, three osteoporotic patients had elevated values and thus appear to represent a separate population. When these subjects were excluded, mean serum iPTH assayed by antiserum GP-1M also was lower than normal (p less than 0.001). The mean value for serum iPTH was lower in osteoporotic patients than in normal subjects when assayed by either antiserum CH-12M (p less than 0.001) or antiserum CH-14M (p less than 0.001). Values for serum phosphate and renal tubular phosphate resorption, both indices of PTH function, were increased (p less than 0.005) in the osteoporotic subjects. Although creatinine clearance decreased with age in both normal and osteoporotic subjects, partial correlations with age held constant showed no relationship between creatinine clearance and serum iPTH. This suggests that a decrease in renal function was not the major factor accounting for the rise in serum iPTH with age. We conclude that serum iPTH increases with aging but that for any given age, it is either normal or low in patients with postmenopausal osteoporosis.

Adult↗

Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: effect of age and dietary calcium.

Intestinal calcium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = -0.22, P < 0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P < 0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH)(2)D were positively correlated (r = 0.50, P < 0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = -0.39, P < 0.01) and with serum 1,25(OH)(2)D (r = -0.50, P < 0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH)(2)D was significantly decreased in both osteoporotic patients and elderly normals (P < 0.001). In osteoporotic patients, calcium absorption increased significantly (P < 0.001) after 7 d administration of a small dose (0.4 mug/d) of synthetic 1,25(OH)(2)D(3). In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH(2)-terminal assay) relative to age-matched controls, and mean serum phosphate was increased. The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH)(2)D contributes significantly to decreased calcium absorption and adaptation in both osteoporotics and elderly normal subjects. In patients with osteoporosis this abnormality could result from a decrease in factors that normally stimulate 1,25(OH)(2)D production, such as the decreased parathyroid hormone secretion and increased serum phosphate demonstrated in this group. In elderly subjects a primary abnormality in metabolism of 25-OH-D to 1,25(OH)(2)D, analagous to that seen in aging rats, cannot be excluded.

Adult↗

Quantitative nuclear-cytoplasmic ratios in human hepatomas.

This report presents quantitative data on nuclear-cytoplasmic (N/C) ratios of human hepatomas, normal liver specimens, and cirrhotic liver specimens. The N/C ratios were determined by point-counting, using an intraocular microscopic grid as the source of the points. The N/C ratios of hepatoma cells were chiefly greater than 0.21, while those of normal and cirrhotic liver cells were chiefly less than 0.21. The N/C ratios of hepatoma cells had a variance significantly greater than those of normal and cirrhotic cells. Quantitative N/C ratios can yield information useful in characterizing cell types for diagnostic purposes.

Biopsy↗

A syndrome of osteoporosis, increased serum immunoreactive parathyroid hormone, and inappropriately low serum 1,25-dihydroxyvitamin D.

Although most patients with postmenopausal osteoporosis have normal or low values for serum immunoreactive parathyroid hormone (iPTH), we have reported previously that a small subset (about 10% of the total group) have increased values. We studied three patients representative of this latter group. Serum iPTH was two to three times higher than the age-adjusted normal mean, serum ionized calcium and total calcium were in the lower half of the normal range, and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] was in the low-normal range. Six months of treatment of one patient with 0.5 microgram/day of synthetic 1,25(OH)2D improved calcium absorption and balance; however, serum iPTH remained high. After surgical removal of 1,010 mg of hyperplastic parathyroid tissue, serum iPTH decreased to normal. These and other data suggest that increased serum iPTH in these patients was caused by secondary hyperparathyroidism, possibly because of inadequate conversion of 25-OH-D to 1,25(OH)2D.

Aged↗

Prospective trial of oestrogen and calcium in postmenopausal women.

In a prospective trial in 72 postmenopausal women to compare the effects on bone loss of no treatment, treatment with oestrogen, and treatment with calcium the women were followed up for at least two years and examined densitometrically and morphometrically. Women in the untreated control group continued to lose bone during the two years, whereas the oestrogen-treated group lost none. Loss in the calcium-treated group was intermediate. Oestrogen appeared to inhibit endosteal bone resorption and may have stimulated subperiosteal bone apposition.

Aged↗