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Biomedical subjects

H K Genant

Publications and source records attributed to H K Genant.

At least 379 records · Page 21Linked to original sources

Bone mineral changes in primary hyperparathyroidism.

We studied 34 patients with primary hyperparathyroidism in order to assess their bone mineral status, to determine its relationship to biochemical parameters (serum calcium and parathyroid hormone) and surgical status, and to determine the relationship between peripheral cortical bone and spinal trabecular bone in this disease. These patients were studied with radiogrammetry of the metacarpals, Norland-Cameron photon absorptiometry of the radius, quantitative computed tomography (QCT) of the spine, industrial radiography of the hands, and conventional radiography of the thoracolumbar spine. We also calculated a spinal fracture index from thoracolumbar spine films. We found that the appendicular measurements correlated well together, but less well with spinal QCT. The spinal fracture index correlated best with QCT (r = -0.55), although significant dispersion was noted. We found that, in general, these hyperparathyroid patients had statistically significant decrements in bone mineral content in both the appendicular and the axial portions of the skeleton. However, the decrement in the appendicular skeleton did not correlate well with that in the axial skeleton. Therefore we conclude that it is necessary to measure both peripheral and central bone mineral content in order to reliably assess the skeletal demineralizing effects of primary hyperparathyroidism in an individual patient.

Adult↗

The effects of bone on proton NMR relaxation times of surrounding liquids.

Preliminary attempts by our group at UCSF to assess fat content of vertebral marrow in the lumbar spine using relaxation time information demonstrated that the presence of trabecular bone affects relaxation times. The objective of this work was a thorough study of the effects of bone on NMR relaxation characteristics of surrounding liquids. Trabecular bone from autopsy specimens was ground up and sifted into a series of powders with graded densities ranging from 0.3 gm/cc to 0.8 gm/cc. Each powder was placed first in n-saline and then in cottonseed oil. With spectroscopy, spin-lattice relaxation times (T1) and effective spin-spin relaxation times (T2*) were measured for each liquid in each bone powder. As bone density and surface to volume ratio increased, T1 decreased faster for saline than for oil. T2* decreased significantly for both water and oil as the surface to volume ratio increased. It was concluded that effects of water on T1 could be explained by a surface interaction at the bone/liquid interface, which restricted rotational and translational motion of nearby molecules. The T1s of oil were not affected since oil molecules are nonpolar, do not participate in significant intermolecular hydrogen bonding, and therefore would not be expected to interact strongly with the bone surface. Effects on T2* could be explained by local magnetic field inhomogeneities created by discontinuous magnetic susceptibility near the bone surface. These preliminary results suggest that water in contact with trabecular bone in vivo will exhibit shortened relaxation times.

Bone Marrow↗

Bone mineral content in early-postmenopausal and postmenopausal osteoporotic women: comparison of measurement methods.

To investigate associations among methods for noninvasive measurement of skeletal bone mass, we studied 40 healthy early postmenopausal women and 68 older postmenopausal women with osteoporosis. Methods included single- and dual-energy quantitative computed tomography (QCT) and dual-photon absorptiometry (DPA) of the lumbar spine, single-photon absorptiometry (SPA) of the distal third of the radius, and combined cortical thickness (CCT) of the second metacarpal shaft. Lateral thoracolumbar radiography was performed, and a spinal fracture index was calculated. There was good correlation between QCT and DPA methods in early postmenopausal women and modest correlation in postmenopausal osteoporotic women. Correlations between spinal measurements (QCT or DPA) and appendicular cortical measurements (SPA or CCT) were modest in healthy women and poor in osteoporotic women. Measurements resulting from one method are not predictive of those by another method for the individual patient. The strongest correlation with severity of vertebral fracture is provided by QCT; the weakest, by SPA. There was a high correlation between single- and dual-energy QCT results, indicating that errors due to vertebral fat are not substantial in these postmenopausal women. Single-energy QCT may be adequate and perhaps preferable for assessing postmenopausal women. The measurement of spinal trabecular bone density by QCT discriminates between osteoporotic women and younger healthy women with more sensitivity than measurements of spinal integral bone by DPA or of appendicular cortical bone by SPA or CCT.

Adult↗

Magnetic resonance imaging of joint disease.

MRI is capable of demonstrating superb anatomic detail of the appendicular skeleton and articulations. Disorders of subcortical bone, cartilage, ligaments, and synovium are being evaluated by MRI. MRI should become an increasingly important diagnostic tool in a variety of articular disorders as technical improvements are made and clinical experience accumulates.

Arthrography↗

Magnetic resonance imaging of osteonecrosis.

Because the available preliminary data strongly indicate that MRI is accurate in diagnosing osteonecrosis, MRI of the hips is recommended in patients suspected of having osteonecrosis, especially if other diagnostic studies are equivocal. MRI also may be useful in following patients who have strong risk factors for osteonecrosis, such as corticosteroid therapy, femoral neck fracture, traumatic femoral head dislocation (Fig. 13), slipped capital femoral epiphysis (Fig. 14), and congenital hip dislocation. In diseases such as systemic lupus erythematosus, both hips eventually may become involved in 50 to 80 per cent of cases. Therefore, the unaffected hip of patients with systemic lupus erythematosus and unilateral nontraumatic osteonecrosis of the hip should be monitored regularly with MRI. The hope is that early diagnosis and treatment of femoral head osteonecrosis will prevent the relentless progression to subchondral collapse and disabling arthropathy. MRI also may be useful in staging patients known to have osteonecrosis. The ability of MRI to image directly in multiple planes facilitates the determination of the volume and location of infarcted segments of bone. This information is important in planning any of the surgical procedures used relatively early in the disease, such as core decompression, rotational osteotomy, or bone graft. Moreover, MRI may prove helpful in evaluating the effectiveness of any therapeutic intervention.

Adrenal Cortex Hormones↗

Magnetic resonance imaging of musculoskeletal neoplasms.

MRI has been shown to be very useful in the work-up of musculoskeletal neoplasms. The lack of ionizing radiation, the superb contrast resolution, and the ability to directly scan the sagittal and coronal planes make MRI a very attractive imaging mode for treatment planning. With spin-echo MRI, maximum contrast between tumor and fatty tissues generally occurs with short TR and TE times (T1-weighted images). Likewise, maximum contrast between tumor and muscle, tendon, or ligaments occurs with long values of TR and TE (T2-weighted images). Early experience suggests that the already exceptional contrast resolution seen with MRI can be improved even more with the administration of intravenous contrast agents. Just as with CT, fatty tumors can usually be easily distinguished from other tissue types with MRI by means of their differential intensity behavior at different pulse sequences. Fluid-filled tumors, such as unicameral bone cysts or aneurysmal bone cysts may be suspected in the same manner, especially if a fluid-fluid level is seen within the lesion. Otherwise, MRI has not been useful so far in noninvasively determining the histologic type of tumors. Our experience and that of others suggests that MRI is equal or superior to CT in the work-up of musculoskeletal neoplasms. This is especially striking when it is remembered that one is comparing an immature MRI technology with a mature CT technology. Although CT presently has a central role in the staging of musculoskeletal tumors, MRI will shortly supplant it in many cases.

Adult↗

Greater vertebral bone mineral mass in exercising young men.

Peak bone mass at skeletal maturity may be an important factor in the relative quantity of skeletal mass in old age. We have studied bone mineral in 46 young men, 28 of whom engage in regular and vigorous exercise programs. Spinal trabecular bone mineral density and spinal integral bone mineral content are significantly greater in the exercise group as compared with the 18 control subjects. Of the exercise group, subjects participating in both aerobic and weight-bearing regimens have the greatest spinal bone mineral mass, followed by those engaging in strictly weight-bearing exercise and those in a primarily aerobic program. An analysis of variance across all subject groups, including the control group, shows a significant difference in spinal trabecular bone density based on the type of physical activity.

Adult↗

Reproducibility of multiple-observer scoring of radiologic abnormalities in the hands and wrists of patients with rheumatoid arthritis.

Forty-one coded radiographic films from 16 patients with rheumatoid arthritis were read by 13 observers, using 4 different methods for scoring abnormalities. Although absolute scores differed widely among individual observers, correlation coefficients were greater than 0.850 for approximately 2 of 3 comparisons. When films were ranked, using the median rank of all readers, 72% of individual ranks were within 10% of the median ranks. Among serial films on individual patients, 92% of comparisons between early and late films were interpreted as demonstrating progression of abnormalities when mean standardized scores showed an increase in scores of 15 units or greater. Films with lesser changes were interpreted inconsistently. This study shows good general agreement among readers in scoring radiologic abnormalities of hands and wrists, when applied to a film set showing a broad spectrum of severity, and defines the sensitivity of radiologic detection of disease progression.

Adult↗

How many joints in the hands and wrists should be included in a score of radiologic abnormalities used to assess rheumatoid arthritis?

Numerous methods for reading abnormalities of rheumatoid arthritis in hand and wrist radiographs have been proposed over the past several decades. There are many differences among these methods, one of the more striking of which is the variation in the number of joints that are scored. In this study, we tested the number of joints that need to be read in order to represent abnormalities accurately and reproducibly, using the scores of multiple observers. Thirteen rheumatologists and radiologists each read a set of 41 hand and wrist films from patients with rheumatoid arthritis. Ten of 13 readers scored 27 joints in each hand and wrist; the other 3 readers scored fewer areas. Fourteen combinations of joints were selected based on the frequency of involvement and the technical adequacy of routine films in assessing a given area. After testing these 14 different combinations, 1 scheme, which included 17 areas read for erosions and 18 areas read for joint space narrowing, was tested further. The correlation coefficients for 10 intraobserver scores derived from this modified scheme compared with the original scores were between 0.981 and 0.997. Seventy-one of 78 interobserver comparisons were better using the new scheme than using the original scheme. These data indicate that the simplified scheme, using a combination of 17 joints to score erosions and 18 to score joint space narrowing, more accurately reflects the extent of abnormalities perceived by a panel of experts than does the original scheme. This abbreviated number of joints shortens the amount of time required to read a set of films and simplifies the scoring of films, since a number of areas that are difficult to read are eliminated from radiographic assessment.

Arthritis, Rheumatoid↗

Quantitative computed tomography for prediction of vertebral fracture risk.

Vertebral trabecular mineral content and peripheral cortical bone mineral were measured in 94 female and 44 male osteoporotic patients and compared to vertebral mineral values obtained for 323 control subjects in a cross-sectional study. The rate of change of spinal trabecular mineral with age (measured by quantitative computed tomography) in control females averaged 1.2% per year from age 20 to 80, with an accelerated loss demonstrated at the menopause. Trabecular bone mass in male controls declined an average 0.72% per year. Female osteoporotics had a mean decrement of 48 mg cm-3 (39%) compared to age-matched controls, whereas males were decreased 66 mg cm-3 (50%). Radial cortical bone was correlated with spinal mineral in osteoporotics for both males (r = 0.48) and females (r = 0.62). Vertebral compression fractures or wedging was generally absent in patients with vertebral mineral values above 110 mg cm-3, whereas almost all patients with values below 65 mg cm-3 had fractures. Quantitative computed tomography for measurement of vertebral trabecular bone mineral density is useful for defining those patients in whom the risk of vertebral fracture is increased.

Adult↗

Theoretical considerations for optimizing intensity differences between primary musculoskeletal tumors and normal tissue with spin-echo magnetic resonance imaging.

In the radiographic assessment of primary musculoskeletal tumors, it is important for therapy planning to accurately define the extent of a tumor. Using a double spin-echo pulse sequence, the T1 and T2 relaxation times and relative hydrogen densities of several neoplastic tissues and of several normal tissues in four patients were measured. Neoplasms measured included one fibrosarcoma, two osteosarcomas, and one giant cell tumor. Normal tissues measured included normal muscle, fat, and bone marrow. Using a mathematical model of the double spin-echo pulse sequence, the intensity difference between each tumor and each normal tissue for multiple values of TR and TE was calculated. These calculated intensity differences were then used to plot isodifference contour curves for each tissue pair. These plots enabled us to pick combinations of TR and TE that optimized the signal difference between tumor and normal tissue. When comparing tumor with predominantly fatty tissue such as marrow or subcutaneous fat, optimal signal difference in our imager occurred at a TR of 600 to 800 msec and a very short TE. When comparing tumor with muscle, optimal signal difference occurred with very long TR times, and TE times ranging from 30 to 90 msec. These preliminary results suggest that an optimal scanning protocol for primary musculoskeletal tumors should contain at least two different pulse sequences with widely separated TR values (500 and 2000 msec in our instrument), and short to intermediate values of TE (28 and 56 msec in our instrument). It is believed that analysis of isodifference contour plots is a useful method for optimizing intensity differences between any two tissue types.

Bone Neoplasms↗

Magnetic resonance imaging and spectroscopy of the periarticular inflammatory soft-tissue changes in experimental arthritis of the rat.

Arthritis was induced in rats by intradermal injection of Freund's complete adjuvant. MRI was performed with a resistive imager operating at 0.35 T. A spin echo (SE) technique with TR = 0.5 and 2.0 seconds, TE = 28 and 56 msec was used. Transaxial images of hindpaws and knees were obtained at different times after injection of adjuvant. In vitro proton spectroscopy of normal and arthritic hindpaws was also performed. Histologic confirmation was obtained in each case. Inflammatory soft-tissue lesions were seen as focal areas of high intensity on spin echo images obtained with TR = 2.0 seconds and TE = 56 msec and were characterized by long T1 and T2 relaxation times and high spin density. In comparison with both conventional radiography and physical examination, early soft-tissue changes were detected more frequently by MRI. This study suggests that MRI is likely to be of value for the early diagnosis of arthritis.

Animals↗

Bone marrow imaging: magnetic resonance studies related to age and sex.

Measurements of T1 and T2 relaxation values and spin density of the lumbar vertebral bone marrow were performed in 212 patients, and the results were correlated with the patients' age and sex. T1 and T2 relaxation times for bone marrow in the lumbar vertebral bodies showed a progressive decrease with age for both sexes (except for the T2 relaxation values in female patients). The replacement of hematopoietic marrow by fatty marrow could explain the decrease in T1 and T2. The T1 and T2 values were in the same range for the first two age groups (age 1-10 years and age 21-40 years) and became slightly greater for the older female patients (age 51 years and older) than for the older males. This could be due to the loss of bone and mineral content, which is more rapid and significant for women. These normal T1 and T2 values may provide a baseline for future evaluation of diseases involving the lumbar spine.

Adolescent↗

Multinuclide digital subtraction imaging in symptomatic prosthetic joints.

One hundred eleven patients with symptomatic prosthetic joints (86 hips, 23 knees, and two shoulders) were evaluated for prosthetic loosening and infection by combined technetium-99m-MDP/gallium-67 digital subtraction imaging. Clinical correlation was based on the assessment of loosening and bacterial cultures obtained at the time of surgery in 54 patients, joint aspiration cultures obtained in 37 patients, and long-term clinical follow-up for greater than 1.5 years in an additional 15 patients. Results revealed an 80%-90% predictive value of a positive test for loosening, and a 95% predictive value of a negative test for infection. However, because of the low sensitivities and specificities observed, this approach to the evaluation of symptomatic prosthetic joints does not seem cost effective.

Adult↗

Long-term estrogen replacement therapy prevents bone loss and fractures.

Although several case-control studies have shown an inverse association between postmenopausal estrogen use and fractures, quantitation of fracture incidence has been lacking. To quantify the degree to which estrogen replacement therapy prevents postmenopausal osteoporosis, a retrospective study was done comparing the occurrence of fractures in 245 long-term estrogen users and 245 case-matched controls, followed for an average of 17.6 years. Quantitative bone mineral assessments were obtained from 18 women using estrogen replacement therapy and their controls (average age, 73 years). Osteoporotic fracture incidence in estrogen users was 50% as great as in the controls (p less than 0.01). Estrogen users showed significantly greater bone mineral: 54.2% greater spinal mineral (p less than 0.0002), 19.4% greater forearm mineral (p less than 0.0005), and 15.6% greater metacarpal cortical thickness (p less than 0.005). Long-term estrogen replacement therapy confers significant protection against bone loss and fracture.

Bone Resorption↗

Bone disease in alcohol abuse.

We evaluated bone disease in eight white men between the ages of 49 and 61 years who had been abusing alcohol for at least 10 years. The mean density of vertebral cancellous bone was 58% of normal, whereas the mean density of appendicular cortical bone was 90% of normal. Marked reduction in active bone resorption and bone formation was seen without evidence of osteomalacia. Serum levels of calcium and magnesium were in the lower range of normal; serum levels of phosphorus, calcifediol, and calcitriol were normal; and serum levels of parathyroid hormone and nephrogenous cyclic adenosine monophosphate were in the higher range of normal. These data suggest that bone disease in these subjects is not due to inhibition of parathyroid hormone secretion or function, or abnormal vitamin D metabolism, but to an inhibition of bone remodeling by a mechanism independent of the calciotropic hormones.

Adult↗