Biomedical subjects
Publications and source records attributed to J M Lane.
The clinical presentations of osteopenic syndromes are differentiated, and a variety of invasive and noninvasive diagnostic studies are compared. Once the diagnosis has been confirmed, treatment options may be selected, including calcium supplementation, exercise, and hormonal therapy.
The serum lactase dehydrogenase (LDH) of 56 patients with Ewing's sarcoma was examined to determine the use of LDH as a tumor marker. The initial LDH level was used to determine its ability to predict survival. The follow-up LDH level also was examined, as an indicator of recurrent disease. The initial LDH level was found to have no prognostic value. Both patients with elevated and normal LDH levels had the same survival rate. The LDH level at recurrence was significantly higher, however, than the follow-up LDH level of those without recurrence (P less than 0.001). The LDH level was most sensitive as a tumor marker for recurrent disease in those patients with multiple sites of tumor involvement at the time of recurrence.
The clinical features and results of 34 patients with chordomas treated over a seven-year period were analyzed. Surgical treatment consisted of wide local excision (n = 6), marginal resection (n = 5), intralesional resection (n = 20), and biopsy (n = 3). Eighteen patients received postoperative radiotherapy. The local recurrence rate was 65%, with 30% of patients developing distant metastases. With the introduction of computed tomography, smaller tumors are currently being diagnosed; as a result, 35% of the patients in this series are disease free, compared with 10% described previously.
It has been suggested recently that, although fluoride therapy may decrease the occurrence of vertebral fractures, it could increase the risk of hip fractures. To evaluate this possibility, we combined retrospective data from five medical centers that have had a large experience with this therapeutic regimen. In 416 osteoporotic patients who were followed for more than 1,000 patient-years of fluoride treatment, there were 17 nontraumatic hip fractures. This incidence of 1.6% per year is similar to the incidence, 1.9% per year, for 120 of the patients in this series who had been followed prospectively for 3 years prior to initiation of fluoride therapy. The expected incidence for women of the same age in the general community is 0.5% per year. Thus, untreated osteoporotic women are at increased risk for hip fracture, but treatment with fluoride seems neither to decrease nor to increase the incidence of hip fracture substantially.
The changes in proteoglycan molecules during the initial stages of fracture healing in rats were characterized. Following extraction of callus proteoglycan components with dissociative solvents, the components were purified in a cesium chloride density gradient. The recovered proteoglycans were characterized with respect to their molecular size distribution using gel filtration chromatography and a centrifugal transport methodology. During this early healing period, a decrease was observed in the relative proportion of the aggregate and in the hydrodynamic size and sedimentation coefficients of these molecules. While some molecular degradation could have occurred during the early stages of fracture healing, the dominant change of the proteoglycan molecules seemed to be disaggregation. No significant difference was observed in the proportion of aggregates reformed when exogenous hyaluronate and link glycoproteins were allowed to interact with the two corresponding monomer preparations. The molecular changes of the proteoglycan molecules seem to parallel those occurring during endochondral calcification of rat epiphyseal cartilage.
Selenium deficiency has several known biochemical effects. In the rat, these effects include loss of glutathione peroxidase (GSH-Px) activity, increased plasma glutathione concentration and increased liver glutathione S-transferase (GSH S-Tr) activity. The time course of the development of these changes in rats fed selenium-deficient diets and the time course of reversal of these changes in selenium-deficient rats fed graded levels of selenium were determined. As selenium deficiency was produced, liver cytosolic and plasma GSH-Px activities decreased first and were less than 5% of control when plasma glutathione concentration and liver GSH S-Tr activity began to increase. Elevated liver GSH S-Tr activity in selenium-deficient rats was corrected by refeeding selenium at the lowest level of supplementation (0.015 ppm) for 4 wk. GSH-Px activity required a supplementation of 0.10 ppm selenium for correction to control levels in 4 wk. Based on these studies a classification of the severity of selenium deficiency into mild, moderate and severe categories is proposed. In addition, the effect of dietary sulfur amino acid supplementation on plasma glutathione concentration was studied.
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We have discussed the biomechanical and biomaterial properties of bone with emphasis on the microenvironment. The microdensity of bone tissues determines the resistance to compressive forces (strength = density2). The structural orientation of bone determines the ability of bone to withstand torsion and bending forces. Highly remodeled bone is brittle and fractures easily because of the multiple reversal planes within the bone plates. Conversely, augmentation of bone on the periphery by modeling leads to increased material microstrength and structural macrostrength. Consequently, appositional modeling augments whereas remodeling diminishes bone strength. Hip fractures, spinal fractures, Colles' fractures, and pelvic fractures have been discussed in terms of their pathophysiology and treatment. An algorithm (Fig. 4-7) has been presented for the differential diagnosis of patients with recently discovered spinal compression fractures. Lastly, a discussion of exercise demonstrated its beneficial role, especially in the retention of bone mass.
The survival of patients with bone sarcomas has improved dramatically with the advent of modern chemotherapeutic regimens, fostering a present trend toward limb sparing procedures. In skeletally immature patients, prosthetic replacement of resected bones and joints is unrealistic because of continued expected growth in the limbs. A stump-lengthening procedure, the reduction-rotation-plasty, has become a valuable alternative to high above-knee amputation. A rhombus-shaped skin incision around the thigh and calf, originally described by Kotz and Salzer, led to a significant discrepancy of the circumference of the proximal and distal skin borders. A circumferential skin incision at the midthigh and a fishmouth-shaped incision at the upper calf was designed to decrease this disproportion. This incision has been used in five consecutive patients with osteosarcoma about the knee. The cosmetic results were excellent, prosthetic fittings were facilitated, and neither vascular nor wound healing problems were encountered.
A number of osteogenic, osteoinductive, and osteoconductive substances currently are being investigated for use in bone repair. It is conceivable that a selected combination of osteogenic cells, osteoinductive factors, and osteoconductive matrices can be combined and fabricated into an implantable material custom-suited to particular clinical demands. Consequently, it is crucial that potential graft substances be experimentally characterized in terms of their precise contribution to the bone-forming mechanisms. In this article, the authors review current areas of research in the realm of experimental grafting, including the current understanding of materials that manifest osteogenic, osteoinductive, or osteoconductive properties.
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Soft tissue sarcomas of the antecubital and popliteal space often involve the neurovascular bundle and are prone to recurrence after surgical resection. Amputation has frequently been performed for control of these tumors. A multimodality treatment program consisting of limb-sparing resection, tumor-bed radiation using temporary iridium 192 implants, and adjuvant chemotherapy for high-grade lesions, has yielded satisfactory preservation of limb function and no local tumor recurrence in ten patients after a median follow-up time of 5 years. Eight of the ten patients are still alive, five of whom beyond 5 years; six of the eight survivors had high-grade tumors. These results are superior to those of 14 patients with similar tumors treated earlier by surgery alone: seven by amputation and seven by soft part resection; four of the latter resulted in local recurrence and all of the seven who had high-grade sarcoma died of disease. Multimodality treatment including limb-sparing resection merits consideration in the management of antecubital and popliteal soft tissue sarcomas.
A nonimmobilized rat tibial fracture model of endochondral osseous repair was examined for the unique localizations of specific collagen genetic types. At various stages of the healing process, the demineralized callus was reacted with immunofluorescent antibodies directed against the type specific forms of matrix collagen. Type III collagen rapidly appeared (day 8-10) and remained in the primitive mesenchymal callus until remodeled. It was particularly prominent in the highly vasoformative regions and the pericallus encapsulation but not present in preexisting cortical and neoformed lamellar bone. The type II collagen, a marker of cartilage, was uniquely located only in areas of chondroid differentiation and calcification. Type II collagen was absent from all bone and was not identified beneath the repairing intact periosteum. The differentiating chondrocytes synthesized type II collagen on an underlayer of type III collagen already within the mesenchymal matrix. From these studies of genetically unique collagen markers, it appears that only in areas of motion or anoxia does an intermediate of chondroid tissue appear. The utilization of specific type II and type III collagen immunofluorescent antibodies has facilitated the understanding of the fracture repair process and has acted as an indicator for unique matrix components.
Because reports have appeared suggesting that hyperbaric O2 treatment protects against the hepatotoxicity of CCl4 in humans, studies were undertaken in rats to assess this possibility and to explore its mechanism. Treatment with 2 atm of O2 for 6 h after intragastric administration of CCl4 (2.6 mmol/100 g) improved survival from 31% to 96%. The same treatment administered 24 h after the CCl4 improved survival from 36% to 50%. The protective effect does not appear to be mediated through changes in excretion or distribution because exhalation of CCl4 was not increased, and hepatic CCl4 concentration was not decreased by hyperbaric O2. Changes in CCl4 metabolism were observed, which could explain the protection. Hyperbaric O2 treatment inhibited in vivo conversion of CCl4 to its volatile metabolites CHCl3 and CO2 by 52% in the 10 h following CCl4 dosing. The predominant effect was on CO2, which is quantitatively the more significant metabolite. Studies with hepatic microsomes isolated from these rats demonstrated that hyperbaric O2 treatment diminished their capacity to metabolize CCl4 to CO2, and O2-dependent process. It had no effect on the metabolism of CCl4 to CHCl3, an O2-inhibited process. These results indicate that hyperbaric O2 suppresses the microsomal mechanism for metabolizing CCl4 in the presence of O2. Because the mechanism of CCl4 hepatotoxicity is thought to be the same in the rat and in humans, hyperbaric O2 therapy is recommended for treatment of CCl4 poisoning in humans.
Guarded optimism could be clearly stated for the treatment of osteogenic sarcoma. Improved methods of diagnosis and staging have been made possible by the computed tomography (CT) scan and other new modalities. The advent of pre- and postoperative chemotherapy has significantly enhanced survival rates that are now approaching 85%. Improved concepts of en bloc resection and better reconstructive techniques suggest that limb salvage procedures are not only possible but can provide excellent functional results in the context of muscle loss. Continued work must be directed toward improving the reconstructive techniques to provide implants with permanence, particularly for young patients and to clearly define the indications for such procedures. Patients presenting with thoracic lesions, although difficult to treat, can expect a 30%--45% long-term survival following repetitive thoracotomies.
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We studied the records of twenty-nine patients with forty-one metastatic lesions of the hand or foot. In five patients the lesions mimicked a benign condition, and inappropriate treatment was given. In eleven patients the acrometastases were the first indication of malignant disease, and four other patients had no known primary malignant lesion. Amputation of a phalanx, digit, or ray is recommended for most solitary phalangeal, metacarpal, or metatarsal lesions when the expected period of survival of the patient exceeds a few months.