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Biomedical subjects

J M Lane

Publications and source records attributed to J M Lane.

At least 55 records · Page 3Linked to original sources
PubMed1997

Osteoporosis. Medical prevention and treatment.

Osteoporosis is a bone disorder characterized by deficient bone mass and fragility fractures of the hip, wrist, and spine. The therapeutic strategies for treating osteoporosis are designed to maximize peak bone mass through proper nutrition, appropriate intake of calcium and vitamin D, maintenance of physiologic menstrual cycles, and a program of weight bearing and strengthening exercises. For the conditions of high bone turnover--osteoporosis in which osteoclastic resorption is increased--efficacious treatment options include hormone replacement therapy, calcitonin, and bisphosphonates. Osteoporosis with low bone turnover results from deficient osteoblastic bone formation and responds to the experimental drug programs of fluoride, parathyroid hormone, and parathyroid hormone related peptide analogues. Determination of bone density defines the patient's current condition, measurement of the level of N-telopeptides (collagen breakdown products) predicts the patient's future regarding osteoporotic fractures, and the presence of risk factors for hip fracture establish the therapeutic window for treatment.

Adolescent↗
PubMed1997

Future directions. Augmentation of osteoporotic vertebral bodies.

Because current medical and surgical treatments of vertebral body fractures are less than adequate, there is a need for interventions that decrease the likelihood of occurrence of these fractures and improve the treatment options once they have occurred. One such broad category of intervention involves the fortification or augmentation of the vertebral bodies. In addition to prophylactically stabilizing osteoporotic vertebral bodies at risk for fracture, augmentation of vertebral bodies that have already fractured may prove to be useful by reducing pain, improving function, and preventing further collapse and deformity. Vertebral body augmentation can also be used as an adjunct to fixation of internal hardware--for example, pedicle screws-in osteoporotic spines. A number of products are now available or are in clinical trials. The most promising products are injectable materials-polymethylmethacrylate or mineral bone cement. The early clinical results using polymethylmethacrylate in percutaneous vertebroplasty for fractured vertebral bodies and the results in vitro using an injectable mineral cement for vertebral body fortification are encouraging. Although the principle of vertebral body augmentation remains encouraging, data to support the widespread use of these techniques remain sparse, and the indications for their use should be more clearly defined.

Bone Cements↗
PubMed1997

Dizocilpine maleate, an N-methyl-D-aspartate antagonist, inhibits dipsogenic responses and C-Fos expression induced by intracerebral infusion of angiotensin II.

The interactions between dizocipline, an N-methyl-D-aspartate open channel antagonist, and the induction of water drinking and c-fos expression by intracerebroventricular (i.c.v.) infusion of angiotensin II have been studied. Pretreating male rats with i.c.v. dizocilpine maleate (100 or 300 nmol) or tenocyclidine (150 nmol), both non-competitive N-methyl-D-aspartate antagonists, inhibited the subsequent dipsogenic response to i.c.v. angiotensin II (125 or 50 pmol, 5-10 min later). Dizocilpine also decreased the angiotensin II-evoked expression of c-fos in the median preoptic nucleus, supraoptic nucleus and the medial (parvicellular) and lateral (magnocellular) parts of the hypothalamic paraventricular nucleus, as well as in the nucleus of the solitary tract and the lateral parabrachial nucleus. Double staining showed that suppression of c-fos expression occurred in N-methyl-D-aspartate R1 receptor containing neurons in the hypothalamus. Pretreating rats with any of three competitive glutamate antagonists (2-amino-5-phosphonopentanoic acid, 60 or 160 nmol; gamma-D-glutamylglyine, 400 nmol; (DL-3/(R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, 0.1 nmol) or the glycine site antagonist 7-chlorokynurenic acid had no effects on angiotensin II-induced drinking. Neither did pretreating rats with the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist 6-cyano-7-nitroquinoxaline-2,3-dione [two infusions, 30 min (240 nmol) and 5 min (160 nmol) before angiotensin II]. To eliminate cross-reactivity of dizocilpine with nicotinic receptors, animals were pretreated with nicotinic acetylcholine blocker mecamylamine (250 nmol, i.c.v.), but this had no effect on angiotensin II-dependent drinking or c-fos expression. These results suggest that an N-methyl-D-aspartate-type glutamate receptor is implicated in the dipsogenic and cellular responses to i.c.v. angiotensin II, and point to the existence of a novel set of interactions between excitatory amino acids and this neuropeptide.

Angiotensin II↗
PubMed1997

Increased sodium appetite stimulates c-fos expression in the organum vasculosum of the lamina terminalis.

The relation between c-fos expression in the forebrain of Lister hooded rats and water and NaCl intakes was examined in response to systemic injection of angiotensin II, desoxycorticosterone, angiotensin II and desoxycorticosterone together, frusemide or low sodium diet, all treatments that induce a sodium appetite. Angiotensin II (1 mg/kg subcutaneously) caused significant increases in the 1-h intakes of water and 1.8% NaCl compared to controls, the effect on water intake being the greater. There was a similar increase in NaCl intake after four days' treatment with desoxycorticosterone (20 mg pellet subcutaneously) but water intake was not increased. The NaCl intake of rats given angiotensin II following desoxycorticosterone treatment was approximately the sum of the intakes after angiotensin II or desoxycorticosterone alone, but the water intake was slightly less than after angiotensin II alone. Frusemide pretreatment (4 mg/kg subcutaneously) caused an NaCl intake similar to that following angiotensin II and desoxycorticosterone but water intake was little affected. Low dietary sodium also increased salt appetite, as expected. These treatments were repeated in rats that were not allowed to drink NaCl, after which the brains were processed for c-fos immunocytochemistry. This showed intense staining of the subfornical organ, median preoptic nucleus, organum vasculosum of the laminal terminalis, paraventricular nucleus and supraoptic nucleus after subcutanous angiotensin II. Animals given angiotensin II following desoxycorticosterone pretreatment showed patterns of c-fos expression that did not differ from those of angiotensin II alone. Treatment with desoxycorticosterone alone produced intense staining in the organum vasculosum of the laminal terminalis and some staining in the median preoptic nucleus. Frusemide gave a similar pattern of staining to desoxycorticosterone, stimulating c-fos expression in the same regions but to a lesser extent. A low salt diet resulted in increased c-fos expression only in the organum vasculosum of the laminal terminalis. Therefore, five different treatments that induced increased sodium appetite evoked distinct patterns of c-fos expression in the anteroventral region of the third ventricle of the rat forebrain. Since the common feature was induction of c-fos in the organum vasculosum of the laminal terminalis, these results suggest a key role for this structure in the development of increased sodium appetite.

Angiotensin II↗
PubMed1997

Stride analysis after proximal tibial replacement.

Ten patients who had undergone primary intraarticular proximal tibial replacement between April 1985 and December 1994, and had a minimum of 2 years of followup, were available for stride analysis. Mean age, time since intraarticular proximal tibial replacement, height, and weight were 23.8 years, 6.5 years, 167 cm, and 63 kg, respectively. A volunteer control group of five male patients who had undergone above knee amputation was obtained from the local community. The mean age, time since above knee amputation, height, and weight were 43.6 years, 24.1 years, 165 cm, and 70 kg, respectively. Stride analysis was performed over the central 6-m portion of a 10-m walkway at a self selected, comfortable pace. Gait velocity, stride length, cadence, and stance time symmetry were measured. Velocity after intraarticular proximal tibial replacement versus above knee amputation was 79.2 +/- 7.6 m per minute versus 71.4 +/- 5.4 m per minute. Cadence after intraarticular proximal tibial replacement versus above knee amputation was 112.4 +/- 10.6 steps per minute versus 110.1 +/- 2.4 steps per minute. There were no significant differences between stride length (1.41 +/- 0.13 m versus 1.43 +/- 0.12 m) and stance time symmetry (0.90 +/- 0.07 versus 0.87 +/- 0.11) for intraarticular proximal tibial replacement versus above knee amputation. The results suggest that endoprosthetic reconstruction resulted in a gait comparable with that after above knee amputation with an external prosthesis.

Adolescent↗
PubMed1997

Morphology and matrix composition during early tendon to bone healing.

This study outlines the early morphologic phenomenon of tendon to bone healing in the rabbit model. Twelve skeletally mature, male New Zealand White rabbits received transplantation of the hallucis longus tendon into a 2-mm calcaneal bone tunnel. The morphologic characteristics of the healing tendon to bone interface were evaluated at 1, 2, 4, and 6 weeks after surgery by the use of conventional histology and immunohistochemical localization of collagen Types I, II, and III. Histologic analysis illustrated progressive maturation and reorganization of the tendon to bone interface with subsequent development of tissue collagen fiber continuity between the tendon and bone. Initially, diffuse immunolocalization of all three collagen types was observed within the scar tissue filling the space between the tendon and bone. During a 6-week period, reorganization of the scar tissue into an interface occurred, similar to an indirect insertion. Although a definitive fibrocartilage region did not form, Type II collagen was localized at the remodeling insertion site throughout the first 6 weeks of repair. In addition, Type III collagen fibers, resembling Sharpey's fibers, were noted to span this interface. The characterization of the insertion between tendon and bone is important to the understanding of healing in commonly used orthopaedic grafting procedures, such as anterior cruciate ligament reconstructions.

Animals↗
PubMed1997

Fibroblast growth factor and epidermal growth factor receptors in ligament healing.

Although recent in vivo studies indicate that basic fibroblast growth factor hastens the healing and strength of the medical collateral ligament after injury, in vitro studies with epidermal growth factor and basic fibroblast growth factor have shown increased fibroblast proliferation with the exogenous administration of these growth factors. Using an established spontaneously healing rabbit injury model, the surgical transection of the medial collateral ligament was undertaken in 12 anesthetized male adult rabbits. Immunohistochemical localization using monoclonal antibodies to the basic fibroblast growth factor receptor and epidermal growth factor receptor were used to identify the distribution and relative concentrations of the individual receptors at 3, 7, 14, and 28 days after surgery. Realizing that the trophic effects of basic fibroblast growth factor and epidermal growth factor are determined exclusively by their individual receptors, this study confirms the hypothesis that basic fibroblast growth factor and epidermal growth factor receptor proteins are present and increase during the early stages of medial collateral ligament healing. The understanding of this rabbit ligament injury model has far reaching implications to ligament healing seen in humans. By elucidating the spatial and temporal regulation of the basic fibroblast growth factor and epidermal growth factor receptor proteins, exogenous growth factor therapy, once approved for human use, potentially can be synchronized with maximal protein receptor levels.

Animals↗
PubMed1997

Use of bone morphogenetic protein 2 on ectopic porous coated implants in the rat.

The ability of recombinant human bone morphogenetic protein 2 to remain osteoinductive and stimulate appositional bone formation on a porous coated implant was tested in a rat quadriceps muscle pouch. Implants with or without hydroxyapatite were used to compare the effects on bone formation of two different does (23 micrograms or 46 micrograms) of recombinant human bone morphogenetic protein 2 against controls as evidenced by contact radiography, histologic examination, and backscatter scanning electron microscopic analysis. Cylindrical plasma sprayed porous titanium implants were placed bilaterally within a muscle pouch surgically created in 48 Lewis rats. Implants treated with recombinant human bone morphogenetic protein 2 formed significantly more bone than did control implants independent of the dose or presence of hydroxyapatite. In all implants with bone formation, osteoinduction via endochondral ossification began within 7 days. By 21 days, cartilage largely was replaced by bone and marrow. The results of this ectopic, nonweightbearing in vivo assay suggest that recombinant human bone morphogenetic protein 2 remains biologically active after application to a titanium implant and may be used to enhance appositional bone formation by direct application to the implant surface.

Analysis of Variance↗
PubMed1996

Treatment of femoral Ewing's sarcoma.

BACKGROUND: The treatment of Ewing's sarcoma consists of chemotherapy for systemic and local disease. However, the role of radiation therapy, and/or surgical resection for definitive local treatment has yet to be determined. METHODS: A retrospective review of 32 patients (24 males and 8 females) treated for femoral Ewing's sarcoma between 1970 and 1985 was performed. Patients were divided into 3 treatment groups: chemotherapy and radiotherapy (CR) (10); chemotherapy and surgery (CS) (9); and chemotherapy, surgery, and radiotherapy (CSR) (13). Patients in the CR group received a mean of 5320 centigray (cGy) of radiation and patients in the CSR group received a mean of 3590 cGy. Multiagent cyclophosphamide/doxorubicin based chemotherapy was used in all cases. Surgery consisted of wide resection or amputation. RESULTS: Patients in the CR group had a higher risk of local recurrence than patients in the CS and CSR groups (P=0.02, log rank). The combination of local recurrences and treatment complications necessitated surgery for 7 of 10 CR patients, whereas 1 of 9 and 4 of 13 in the CS and CSR groups required additional surgery. The median survival for the entire group was 39 months. Minimum follow-up for surviving patients was 45 months. Five-year survival consisted of 1 of 10 patients in the CR group, 2 of 9 in the CS group, and 7 of 13 in the CSR group. There were no statistically significant differences among the three survival curves. Tumor location within the femur was a significant prognostic variable. Distal femoral location had a survival advantage compared with proximal and mid-femur locations (P = 0.049, log rank). CONCLUSIONS: Femoral Ewing's sarcoma remains a disease with a poor prognosis. Radiation alone for local treatment results in a high rate of local recurrence and complications. Our current local treatment strategy for femoral Ewing's sarcoma includes surgery in all and adjuvant radiotherapy in many of the patients.

Adolescent↗
PubMed1996

Qualitative and quantitative analysis of orthotopic bone regeneration by marrow.

A rat model of a femoral segmental defect was used to specifically test the hypothesis that autogenous marrow has the osteogenic capability to heal a bone defect. The variables analyzed included the ratio of the marrow volume to the defect, implantation of live or dead marrow, and remodeling of established nonunions by implantation of live marrow. The uniqueness of this model allows biomechanical evaluation of the new bone formed by the implant. When live marrow was implanted, woven bone formed at 3 weeks, progressing to early lamellar bone at 6 weeks, with subsequent remodeling for as long as 12 weeks in a volumetric fashion (p < 0.05). Bone marrow, when placed in a fresh femoral defect and given in sufficient amounts, produced a rate of union comparable with that of autologous bone grafts. Mature lamellar bone formed by marrow was evaluated biomechanically; the results were statistically comparable with those of cancellous bone grafts at 12 weeks. Significant bone formation occurred when marrow was percutaneously injected in femoral nonunions, although union and remodeling did not take place in this rat model. Implantation of dead marrow resulted in rare cellular infiltration and minimal bone formation in a manner comparable with that of autogenous cancellous bone grafts. These results indicate that bone marrow can lead to structurally functional bone regeneration in an orthotopic location.

Analysis of Variance↗
PubMed1996

Primary immunolocalization of estrogen and progesterone target cells in the human anterior cruciate ligament.

To identify estrogen and progesterone target cells in the human anterior cruciate ligament immunohistochemical localization of both estrogen and progesterone receptors was performed in 17 specimens of human anterior cruciate ligament. All ligament specimens were obtained at surgery. Thirteen specimens were from women, and four were from men: the average age was 57 years (range, 18-78 years). Eleven specimens (from nine women and two men) came from total knee replacements for osteoarthritis of the knee: three (from two women and one man), from reconstructions of the anterior cruciate ligament: two (both from women), from medial meniscectomies; and one (from a man), from an amputation secondary to chondrosarcoma of the pelvis. An immunoperoxidase method using monoclonal antibodies to the estrogen and progesterone receptors was employed to identify estrogen and progesterone target cells in the anterior cruciate ligament. Staining of both receptors was demonstrable in 14 specimens and in the remaining three specimens less than 15% of the cells were stained. Both estrogen and progesterone receptors were localized to synoviocytes in the synovial lining, fibroblasts in the anterior cruciate ligament stroma and cells in the blood vessel walls of the ligament. This demonstration of receptors for estrogen and progesterone in the cells of anterior cruciate ligament suggests that female sex hormones may have an effect on its structure and composition.

Adolescent↗
PubMed1996

Total hip arthroplasty.

Total hip arthroplasty continues to be an extremely successful procedure, with ever-widening indications and regular improvement in technique, materials, and design. In the past year several studies were published evaluating the results of both cemented and cementless total hip arthroplasty at mid- to long-term follow-up. In addition, careful analysis of basic laboratory studies including finite-element analyses have added to our understanding of materials and design. Specific findings in the past year included poor results with cemented hips in younger patients at long-term follow-up of greater than 16 years. A lower incidence of loosening has been found for cobalt chrome-cemented components compared with titanium-cemented components. No difference was found in the results of metal-backed versus non-metal backed cemented acetabular components, and an increasing incidence of loosening was shown for cemented acetabular components with time. The newer cementless hip arthroplasties showed evidence of learning curve, particularly with regard to innovative design such as acetabular screw rings, whereas porous-coated hemispherical cups appeared to do well. Thigh pain continues to be a problem with cementless designs, and the controversy of titanium versus cobalt chrome for cementless femoral stem designs continues at full tilt.

Adult↗
PubMed1996

Use of bone morphogenetic protein-2 in the rabbit ulnar nonunion model.

The ability of the osteoinductive protein and recombinant human bone morphogenetic protein-2, combined with polylactic glycolic acid porous microspheres and autologous blood clot to heal a large segmental defect was tested in a rabbit diaphyseal defect model. Two centimeter nonuniting defects were surgically created in the bilateral ulnae of 50 male New Zealand white rabbits. Each defect was then implanted with a pastelike polylactic glycolic acid/blood clot combination that was mixed with 5 different concentrations of recombinant human bone morphogenetic protein-2. The forearms were radiographically assessed on a biweekly schedule for 8 weeks. At 8 weeks, all animals were sacrificed and forearms radiographed. Radiographs were then scored by 3 independent observers for bone formation and union rates. United limbs were tested in torsion for mechanical strength using a Burstein torsion tester. All nonunited limbs were analyzed histologically as were 2 united limbs from each dosage group. Radiographic evaluation revealed that there was a dose dependent response in healing of the ulnar defect with a higher bone formation rate in the 2 higher dose limbs than in the lower dose limbs. Union was achieved in 100% of the highest dose limbs, whereas only 50% of the lowest dose limbs achieved bony union. No defects implanted with carrier alone achieved union. Biomechanical studies revealed significantly stiffer bone than age matched controls. Histologic analysis demonstrated normal bone formation with abundant normal appearing osteoid. These dose response data further support the role of recombinant human bone morphogenetic protein-2 as a potent morphogen in bone regeneration.

Animals↗
PubMed1996

Bone morphogenetic protein-2: biology and applications.

Bone morphogenetic protein-2 is a low molecular weight glycoprotein, classified as a morphogen. The sine qua non of bone morphogenetic protein is consistently reproducible induction of bone development in heterotopic sites. Bone morphogenetic proteins belong to the expanding transforming growth factor-beta superfamily. Bone morphogenetic protein-2 has pleiotropic functions that range from extraskeletal and skeletal organogenesis to bone generation and regeneration. Bone morphogenetic protein induced bone formation in postfetal life recapitulates the process of embryonic and endochondral ossification. Through recombinant gene technology, human bone morphogenetic protein-2 is available in almost unlimited amounts for basic research and clinical trials. Human bone morphogenetic protein-2 induces structurally sound orthotopic bone in a variety of experimental systems, including femoral defects in rats, tibial and ulnar defects in rabbits, femoral defects in sheep, mandibular defects in dogs, spinal fusion in dogs, and porous ingrowth in rats. Human bone morphogenetic protein-2 research extends to the fields of developmental biology, genetics, and evolution. Bone morphogenetic protein has been used successfully at the authors' institution to heal clinical nonunions and to achieve spinal fusion. This report reviews the current understanding of bone morphogenetic proteins in general and BMP-2 in particular and summarizes their potential applications.

Animals↗
PubMed1995

High grade soft tissue sarcoma of the flexor fossae. Size rather than compartmental status determine prognosis.

BACKGROUND: High grade soft tissue sarcoma arising in the popliteal space, axilla, and antecubital fossae (flexor fossae tumors) have by convention been classified as extracompartmental tumors by the accepted staging and grading criteria of the Musculoskeletal Tumor Society (MSTS). Advances in neoadjuvant chemotherapy and radiation therapy have made surgical resection more feasible. The hypothesis to be tested is that compartmental status may not be of prognostic significance if the tumor is adjusted for size, histologic grade, and distant metastasis after undergoing adjuvant chemotherapy and radiation. METHODS: From June 1976 to December 1992, 22 patients with high grade soft tissue sarcomas of the flexor fossae (Group A) were treated at UCLA Medical Center. The histologic subtypes were liposarcoma (five), synovial cell sarcoma (eight), malignant fibrous histiocytoma (four), leiomyosarcoma (two), angiosarcoma (two), and rhabdomyosarcoma (one). The popliteal fossa was the location in 11, the axilla in 10, and the antecubital fossa in 1. Wide resection was attempted in all patients after preoperative chemotherapy and radiation therapy. Amputation was performed in 5 patients because of repeated or extensive recurrent tumor. A group of 77 patients (Group B) with high grade soft tissue sarcoma located within an extremity compartment were chosen to test the hypothesis that survival of patients with tumors in the flexor fossae is equal to that of patients with intracompartmental tumors of similar size and grade if both are given adjuvant therapy. This group was chosen so that histologic subtype, size, sex, and location would be similar in the two groups. The authors selected thigh and calf tumors for comparison with popliteal fossa tumors and periscapular, deltoid, and arm tumors for comparison with axilla and antecubital fossae tumors. All of these patients had similar treatment and follow-up protocols. The median follow-up of survivors in Group A was 104 months and for patients in Group B was 79 months. RESULTS: The 5-year cumulative survival rate (Kaplan-Meier method) of patients in Group A was 76%, and 67% for those in Group B. The difference was not significant. Three patients in Group A (14%) and 17 (22%) in Group B had local tumor recurrence. Eight patients in Group A (36%) and 27 (35%) in Group B had lung metastases. Age, sex, histologic subtype, and surgical margins did not affect survival outcomes, lung metastasis, and local recurrence. However, patients with larger tumors (maximum dimension > or = 8 cm or cross-sectional area > or = 40 cm2) had significantly poorer survival, more metastases, and local recurrences. CONCLUSION: Flexor fossae sarcomas do not have a poorer prognosis than extremity intracompartmental tumors when adjusted for size, distant metastasis, and histologic grade when they are treated with adjuvant radiation therapy, chemotherapy, and surgery.

Adolescent↗
PubMed1995

Design and evaluation of a sterile compounding facility.

The design and evaluation of a sterile compounding center for a large community teaching hospital are described. The new sterile products area was redesigned to improve efficiency by minimizing staff travel and to incorporate recommendations of the ASHP Technical Assistance Bulletin on Quality Assurance for Pharmacy-prepared Sterile Products. The design approach combined strategic planning with master facilities planning. The process began with a systems analysis, followed by the development of a functional program (a comprehensive list of design specifications). Travel studies were performed before and after renovation to determine gains in efficiency; technician travel decreased 29% and pharmacist travel, 42%. The new facility design met the specifications in the functional program and appeared to comply with all recommendations in the ASHP document for all risk levels of preparations.

Drug Compounding↗