Biomedical subjects
Publications and source records attributed to R Lindsay.
A case of childhood affective disorder with episodes of depressive stupor in a 13-year-old pre-pubertal boy is described. Changes in the patient's clinical state were accompanied by changes in the dexamethasone suppression test. A family history of affective illness on the maternal side, with phenomenological similarities, is noted.
A considerable body of evidence has now been assembled demonstrating loss of ovarian function is associated with increased skeletal remodeling and acceleration of bone loss. The available data suggest that this is probably the most significant risk factor of osteoporosis for most women. The presence of other risk factors may well magnify the effect of menopause either by reducing peak bone mass, enhancing rate of bone loss, or by increasing the risk of falls and injury in later life. Estrogen therapy reverses the increased remodeling and reduces the rate of bone loss significantly. Controlled studies have confirmed that this effect persists as long as estrogens are prescribed (at least 10 years) and ceases after therapy is stopped, when there is an acceleration of bone loss that is similar to that following oophorectomy. Consequently, the earlier estrogen therapy is begun, and the longer it is continued, the more effective are the results. The available data suggest that a minimum of 5-10 years treatment may be necessary to reduce the likelihood of hip fracture by about 50%, and vertebral fracture risk may be cut by as much as 90%. Certain progestogens may also inhibit bone loss, but their addition to estrogen in sequential or combination therapy does not appear to modify the effects of estrogen significantly.
This article will review the pathogenesis of osteoporosis and the potential for prevention of the disorder, paying particular attention to estrogens. In addition, it will attempt to provide some rationale for identifying those who may be at risk from the disorder at a time when effective preventive therapy can be instituted, while also reviewing the results of treatment programs for the established disorder.
Explore the source record for details and available documents.
Results from Dual Photon Absorptiometry, a common tool in the assessment of bone mass, vary as a function of source life, increasing by as much as 0.6% per month. This rate of increase may vary with source, and its cause is not clear. However, this long-term "drift" must be considered a significant problem for longitudinal studies and regular standardization of DPA equipment, in addition to calibration to machine standards, may be required for stringent quality control.
A patient with a mesenchymal tumor and hypophosphatemic osteomalacia was studied before and after tumor excision. Initial laboratory values included normal serum calcium, decreased serum phosphorus and tubular reabsorption of phosphate, undetectable 1,25-dihydroxyvitamin D, and normal parathyroid hormone. Histomorphometry of a bone biopsy specimen showed evidence of increased osteoclastic bone resorption. By 16 hours after tumor removal, 1,25-dihydroxyvitamin D level had normalized, but serum phosphorus level was unchanged; at 28 hours, both serum phosphorus value and tubular reabsorption of phosphate were within normal limits. It is concluded that tumor removal is associated with rapid correction both of 1,25-dihydroxyvitamin D production and of renal phosphate wasting. Increased bone resorption suggests the production of an osteoclast activator by the tumor and may explain the typically normal serum calcium value in this disorder.
Many studies have shown that bone loss accelerates after oophorectomy or the menopause. If estrogen replacement therapy is instituted soon after the onset of these changes, much of this bone loss, and subsequent fractures, can be prevented. Most investigations have evaluated the effects of oral estrogens, but other routes of administration may be equally beneficial. The use of estrogens natural to the human also seems preferential. Several theories have been advanced regarding the mechanism of action of estrogen in this population. The most popular concept holds that estrogen stimulates calcitonin production, but other theories also must be considered since this is controversial and far from proven. A local action of estrogen on the skeleton cannot be ruled out. In addition to estrogen, calcium supplementation and exercise may have roles to play in the prevention and management of osteoporosis.
98 post-menopausal women were randomly allocated to either Org OD 14 [(7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one] 2.5 mg/day or placebo. Treatment was continued for up to 6 yr. Any thromboembolic episode that occurred was recorded. Prothrombin time (PT), partial thromboplastin time (PTT), factor VII level and factor X level were measured prior to treatment and at yearly intervals. Antithrombin III level was measured in the last two yr of the study. There was one cerebrovascular accident after 3 months of placebo therapy but no other thromboembolic episodes. No significant difference was found between the effects of Org OD 14 and placebo with regard to any clotting factors at any time interval, although factor VII and factor X levels were consistently lower in the OD 14 group than in the placebo group. Antithrombin III levels measured after 5 and 6 yr were significantly higher (P less than 0.01) in the OD 14 group, suggesting a reduced risk of thrombosis in the treatment group.
Osteoporosis is a major public health problem, particularly for the postmenopausal woman. With the withdrawal of estrogen at menopause, bone resorption begins to exceed formation in remodeling cycles and bone mass is inexorably lost. Clearly, preventing postmenopausal osteoporosis is the aim of management. Individuals with risk factors for developing this condition should have noninvasive bone density determination and should be considered for preventive regimens. Therapeutic options for prevention include calcium, estrogen, and exercise. Once osteoporosis is established, therapeutic options may include those listed previously as well as fluoride and other modalities currently under investigation.
Fibrous hamartoma of infancy is an uncommon fibroproliferative lesion that occurs only in infancy and childhood. The present case is unusual for the presence of two separate lesions, infiltration into the superficial muscle, infiltration and entrapment of nerves, and rapid recurrence after initial surgery. Despite these unusual and suspicious features, follow-up evaluations over the 15 months subsequent to the last resection showed no evidence of recurrence.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Osteoporosis is a major public health problem, and its prevalence may be increasing. Unfortunately, once spinal fractures occur, the treatment of osteoporosis is less than satisfactory. Prevention is thus the preferred approach. To initiate a prevention program would require identification of those at greatest risk. Usually, small, thin, white or Asian women who have had an early menopause (or oophorectomy) can be considered most at risk. Other factors may include low calcium intake, inactivity, alcohol and cigarette consumption, and nulliparity. For those clinically thought to be at greatest risk, bone mass measurements may be used to more clearly define the population for whom preventive therapy would be indicated. Prevention consists of dietary and lifestyle alterations, primarily increases in calcium intake and exercise, and the judicious use of estrogens. Estrogen therapy remains the single most effective method for prevention of bone loss.
Prevention of osteoporosis is clearly the preferred approach, since treatment of the established disorder is less than satisfactory. However, accurate identification of those at risk for fractures is impossible at present. By judicious use of risk assessment and the addition of bone mass measurements in the postmenopausal patient, the physician can define a group of patients who will be at some increased likelihood of subsequent osteoporosis. Since estrogen therapy is the most effective single agent for prevention of bone loss, estrogens can be recommended for this group of patients, if otherwise not contraindicated. The addition of a progestogen to the regimen may add to the effect of estrogen by stimulating bone formation. Estrogen therapy may have other effects in the postmenopausal patient population that must be considered when deciding about the introduction of therapy.
The management of osteoporosis after fracture has occurred is currently difficult. The most effective approach is clearly prevention. Reduction in risk factors, adequate calcium nutrition, and physical activity are all important features, but the mainstay is estrogen therapy. Although this treatment early in the postmenopausal period has been shown to reduce bone and fracture, it must not be forgotten that other biochemical abnormalities in calcium homeostasis may also cause bone loss with aging. Despite the difficulties in treating established disease, newer strategies are being developed in the hope that increments in bone mass may reduce the frequency of fracture recurrence.
Despite the fact that the scanning electron microscope (SEM) offers a number of unique advantages for the investigation of bone structure, this instrument has seldom been applied in studies of the iliac crest bone biopsy. Here we describe a very simple method of preparing iliac crest biopsies for examination in the SEM after the routine histomorphometric analysis has been performed. With observations on biopsies from normal subjects and patients with osteoporosis, the paper illustrates the potential of the method for performing correlative light and scanning electron microscopical studies and for gaining new information on the three-dimensional architecture of trabecular bone.
The effect of brief periods of phosphate administration on indices of human skeletal metabolism was investigated. Thirteen subjects (8 women, 5 men; 19-36 years old) received 2 g of oral phosphate daily for 5 days. Serum phosphorus rose 26% (3.8 +/- 0.1 mg/dl to 4.8 +/- 0.1 mg/dl; p less than .01) while total calcium fell (9.3 +/- 0.1 mg/dl to 8.9 +/- 0.1 mg/dl; p less than .01). Parathyroid hormone levels increased by 50% (14.1 +/- 2.0 pg/ml to 21.5 +/- 1.7 pg/ml; p less than .05) although values remained within the normal range. A persistent phosphaturia (0.64 +/- 0.10 g/g Cr to 1.8 +/- 0.4 g/g Cr; p less than .05) and a 69% fall in urinary calcium (80.8 +/- 10.0 mg/g Cr to 24.6 +/- 6.0 mg/g Cr; p less than .001) were observed. 1,25-dihydroxyvitamin D3 and urinary hydroxyproline concentrations did not change significantly but the bone gamma-carboxyglutamic acid protein (BGP) concentration rose 41% by day 2 (9.6 +/- 1.3 mg/ml to 13.5 +/- 2.2 mg/ml; p less than .005) and remained elevated throughout the study period. These results support the possibility that brief periods of phosphate administration may be useful in the therapy of disorders associated with low bone turnover, such as osteoporosis.
The effects of oral contraceptive use on bone mineral density in pre- and post-menopausal women were evaluated in two separate studies. First, in a population of young women carefully controlled for all risk factors known to be associated with osteoporosis, it was determined that vertebral bone mineral was increased by about 1% for each year of exposure to oral contraceptives. A similar result was obtained by examining vertebral mineral content of an unselected, but healthy premenopausal population. Effects of oral contraceptives on bone mass could not be found among postmenopausal women, unless perhaps in the initial year or two after loss of ovarian function.