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Biomedical subjects

J M Lane

Publications and source records attributed to J M Lane.

At least 73 records · Page 4Linked to original sources

Epidemic gonococcal conjunctivitis in central Australia.

OBJECTIVES: To describe an epidemic of gonococcal conjunctivitis in central Australian Aboriginal children, the responsible phenotypes of Neisseria gonorrhoeae, factors facilitating spread and treatment efficacy. DESIGN: Prospective study of patients with laboratory confirmed or clinical gonococcal conjunctivitis diagnosed from January to July 1991. SETTING: The Alice Springs and Barkly Tablelands Health Districts of the Northern Territory, the Anangu Pitjantjatjara Lands of South Australia and the Ngaanyatjarra Homelands of Western Australia. METHODS: Cases were identified from surveillance data and laboratory notifications, and by active case finding. A community survey explored risk factors. MAIN OUTCOME MEASURES: Age-specific attack rates, auxotype/serovar characterisation of isolates, and clinical response to single dose treatment. RESULTS: We identified 432 cases. The highest attack rate was in the 0-4 year age group (86 per 1000), and the risk of conjunctivitis decreased with age. The odds ratio of secondary infection in household compared with community contacts was 14.5 (P < 0.002; 95% CI, 1.8-120.0). Disease was less common in children with clean faces and hands. The outbreak occurred after unseasonable rains and large community gatherings. Isolates were predominantly IA serovars, less common among central Australian serovars. CONCLUSIONS: The trigger for nonsexually transmitted gonococcal conjunctivitis epidemics remains obscure. Age is a significant risk factor and social and ecological factors may also contribute. Active case finding within affected households and treatment with a suitable penicillin is effective in stopping transmission.

Acute Disease↗

Immunolocalization and expression of bone morphogenetic proteins 2 and 4 in fracture healing.

Recently, it has become increasingly evident that fracture healing involves a complex interaction of many local and systemic regulatory factors. The roles of some of these growth factors have been described; however, little is understood about the presence of the bone morphogenetic proteins in fracture repair, despite the fact that they are the most potent osteoinductive proteins known. This study defines and characterizes the physiologic presence, localization, and chronology of the bone morphogenetic proteins in fracture healing with an established rat fracture healing model. With use of a recently developed monoclonal antibody against bone morphogenetic proteins 2 and 4 developed with standard avidin-biotin complex/immunoperoxidase protocols, frozen undecalcified fracture calluses were analyzed semiquantitatively for the percentage of various types of fracture cells staining positively. During the early stages of fracture healing, only a minimum number of primitive cells stained positively in the fracture callus. As the process of endochondral ossification proceeded, the presence of bone morphogenetic proteins 2 and 4 increased dramatically, especially in the primitive mesenchymal and chondrocytic cells. While the cartilaginous component of the callus matured with a concomitant decrease in the number of primitive cells, there was a concomitant decrease in both the intensity and the number of positively staining cells. As osteoblasts started to lay down woven bone on the chondroid matrix, these osteoblastic cells exhibited strong positive staining. The intensity of this staining decreased, however, as lamellar bone replaced the primitive woven bone. A similar observation was noted for the areas of the callus undergoing intramembranous ossification. Initially, within several days after the fracture, periosteal cells and osteoblasts exhibited intense staining for bone morphogenetic proteins 2 and 4. As the woven bone was replaced with mature lamellar bone, this staining decreased. These data, and the awareness of the strong osteoinductive capacities of bone morphogenetic protein, suggest that bone morphogenetic proteins 2 and 4 are important regulators of cell differentiation during fracture repair.

Animals↗

Bone histomorphometry in men with spinal osteoporosis.

The purpose of this investigation was to determine whether there is an effect of age and the presence of predisposing risk factors on the pattern of bone resorption in men with spinal osteoporosis. We present iliac bone histomorphometric data after in vivo double tetracycline labeling in 21 men aged 34-74 with significant spinal osteoporosis as evidenced by compression spinal fracture without significant trauma. Fourteen of the 21 men (67%) had identifiable predisposing risk factors for their osteoporosis, such as ethanol abuse, hypercortisolism, hypogonadism, or underlying medical conditions. The other 7 men (33%) had no such identifiable risk factors. The conclusions of the study were that (1) there was no correlation between age of the patient and degree of bone resorption based on two parameters of resorption and (2) there was no difference in the pattern of bone resorption between the groups with and without known predisposing risk factors for osteoporosis or underlying medical conditions.

Adult↗

Giant cell tumor of the distal radius.

We compared the outcome of patients with giant cell tumor of the distal radius treated by curettage/cryosurgery and en bloc resection, evaluating oncologic success, functional results, and complications. Thirty consecutive cases of giant cell tumor of the distal radius were treated at our institution between 1958 and 1988. Twenty-six patients were available for follow-up examination, with a minimum follow-up period of 3 years and median follow-up period of 9 years. Primary curettage/cryosurgery had a local recurrence in 3 of 12, and repeat curettage/cryosurgery achieved local control in in 16 of 18 primary and recurrent cases. The major complications in this group included skin necrosis, transient nerve palsies, and fragmentation with carpal collapse. An average of 60% of contralateral range of wrist motion was preserved. Ten patients underwent en bloc excision and arthrodesis for either primary or recurrent tumor; none developed local recurrence. The main complication in this group was failure of internal fixation and non-union at the graft-radius junction. Resultant strength and function were similar in both groups. Intralesional excision with adjunctive cryosurgery is an effective alternative to en bloc excision with the advantage of preserving the distal radius and wrist joint function, but with a notable complication rate. En bloc excision with arthrodesis is more suitable for extensive local disease with poor residual bone stock and as salvage for failed intralesional excision.

Adolescent↗

A custom distal femoral prosthesis for reconstruction of large defects following wide excision for sarcoma: results and prognostic factors.

Between 1979 and 1986, 37 patients with sarcoma of the distal femur underwent limb salvage using a custom prosthetic knee replacement. Thirteen (35%) had early complications. Fourteen (38%) had late complications, which consisted of 6 aseptic femoral loosenings, 1 aseptic tibial loosening, 2 tibial fractures, 2 contractures, 1 femoral fracture, 1 prosthetic fracture, and 1 septic loosening. By 1988, nine patients died. Thirteen prostheses failed in 12 patients, resulting in 9 revisions, 2 above-knee amputations, and 2 Van Nes rotationplasties. The 2- and 5-year prosthetic survival rates were 82% and 57%, respectively. Twenty-two of the 26 survivors (85%) had successful limb salvage. Preventable factors were implicated in the loosening of six femoral components and in one femoral fracture. The mean Hospital for Special Surgery Knee Score was 69 (range: 62 to 86).

Adolescent↗

Collagen in tendon, ligament, and bone healing. A current review.

Cells that produce a particular type of collagen under normal physiologic circumstances can be induced by certain local triggers to change the amount and type of collagen synthesized. This has become most apparent during bone, tendon, and ligament healing, where cells that once produced the collagen of normal intact tissue are induced to synthesize different types of collagen at the repair site of injured tissue. For example, Type III collagen, not a major component of the extracellular matrix in normal tendons, is believed to be of great advantage during the healing process because of its ability to form rapid crosslinks and precariously stabilize the repair site. Although much is known about the gross histologic changes occurring during tissue healing, little is known about the specific role of the individual collagen types or what influences their development. This review addresses the role of collagen in normal and healing bone, tendon, and ligament. Much experimental effort is needed to uncover the distribution and function of the collagen types within connective tissue elements and the effect of growth factors on the phenotype of collagen produced in these tissue, with the ultimate goal of developing clinical manipulations that take advantage of the unique properties of each type of collagen.

Anterior Cruciate Ligament↗

Immunohistochemical detection of bone morphogenetic proteins in bone and soft-tissue sarcomas.

BACKGROUND: Bone morphogenetic proteins (BMPs) are potent inducers of bone formation. Functional and immunohistochemical studies have identified BMPs in a subset of osteosarcomas. In the present study, the authors extend the analysis of BMP expression to other bone and soft tissue sarcomas. METHODS: Monoclonal antibody AbH3b2/17 against human BMP-2 and BMP-4 was used in avidin-biotin-immunoperoxidase assays with frozen sections of bone tumors (71 specimens), soft tissue sarcomas (69 specimens), and normal tissues. RESULTS: Among bone tumors, BMP was detected in osteosarcomas (17 of 29 samples), malignant fibrous histiocytomas (MFHs) (6 of 6), and the spindle cell sarcomatous components of spindle cell (dedifferentiated) chondrosarcomas (4 of 4), but not in conventional chondrosarcomas (0 of 10) or Ewing's sarcomas (0 of 14). Histologic subtypes of osteosarcoma differed for BMP expression, with 8 of 9 fibrohistiocytic, 9 of 13 osteoblastic, and 0 of 5 chondroblastic lesions showing immunostaining. In all BMP-positive bone tumors, immunostaining was localized in the cytoplasm of primitive mesenchymal cells, with little or no staining in tumor matrix and more mature osteoblastic/chondrocytic cells. Among soft tissue sarcomas, MFHs (11 of 12), liposarcomas (5 of 11), leiomyosarcomas (3 of 9), and malignant schwannomas (3 of 8) showed cytoplasmic BMP immunostaining. Synovial sarcomas (0 of 9), rhabdomyosarcomas (0 of 8), and fibrosarcomas (0 of 7) were BMP-negative. All normal human tissues tested, including the tissues of a 16-week-old fetus, lacked BMP immunoreactivity. CONCLUSIONS: Bone morphogenetic protein is expressed in a subset of osteosarcomas, a high proportion of MFHs of bone and soft tissue, and in spindle cell chondrosarcomas. In these tumors, BMP is localized predominantly to the cytoplasm of malignant cells with primitive mesenchymal features; no or little BMP is detected in the more differentiated elements of bone and soft tissue sarcomas. Different histologic types of bone and soft tissue sarcomas may mimic discrete stages of mesenchymal differentiation as defined by BMP expression and histologic criteria.

Antibodies, Monoclonal↗

Expression of bone morphogenetic proteins in human osteosarcoma. Immunohistochemical detection with monoclonal antibody.

BACKGROUND: Bone morphogenetic proteins (BMP) induce ectopic bone formation in vivo and may play a role in normal bone development. In addition, bone morphogenetic activity, as measured in a bone-forming assay in immunodeficient, athymic nu/nu mice, is present in a proportion of osteosarcomas; this activity, which may be mediated by BMP, is correlated with a poor prognosis. METHODS: The development of a monoclonal antibody against recombinant human BMP-2, AbH3b2/17, has allowed immunohistochemical localization of BMP in tumor tissues. Cryostat sections of osteosarcomas (21 tumor samples), chondrosarcomas (5 samples), and Ewing's sarcomas of bone (5 samples) were examined with AbH3b2/17 using the avidin-biotin-immunoperoxidase method. RESULTS: The authors found AbH3b2/17 immunoreactivity in 12 of the 21 osteosarcoma samples (57% sensitivity) obtained from 20 patients. For one patient, samples of the primary lesion and a subsequent metastasis were tested, and only the latter showed AbH3b2/17 immunoreactivity. The chondrosarcomas and Ewing's sarcomas examined showed no immunoreactivity. In antigen-positive osteosarcomas, AbH3b2/17 immunostaining was localized predominantly in the cytoplasm of tumor cells. Moreover, the proportion of AbH3b2/17-reactive cells varied among osteosarcomas with disparate histologic features. CONCLUSIONS: The authors identified a rapid and widely applicable method for detecting BMP expression in intact tissues, which may complement and enhance the bone-forming assay in nu/nu mice as a prognostic procedure in osteosarcomas.

Adolescent↗

The interaction of the macrophage and the osteoblast in the pathophysiology of aseptic loosening of joint replacements.

Macrophage phagocytosis of cement particles with production of inflammatory mediators is a component of the underlying mechanism of aseptic loosening of joint prostheses. Prostaglandin E2 (PGE2), a bone resorbing mediator, has been implicated in the loosening process. Investigations have shown that macrophage phagocytosis of cement particles leads to production of bone-resorbing mediators other than PGE2. In this study, conditioned medium from macrophages exposed to crushed simplex cement particles stimulated osteoblasts to release radiolabeled arachidonic acid and metabolites. Incubation of osteoblasts in conditioned medium from macrophages exposed to cement particles small enough to be phagocytized increased PGE2 release 80-fold over unexposed osteoblasts (P < 0.001). Incubation of osteoblasts in conditioned medium from macrophages exposed to particles too large to be phagocytized, or to bone cement filtrate, did not stimulate PGE2 release. We propose that the role of the macrophage in aseptic loosening is primarily to recognize the mechanical failure of the cement mantle by phagocytosis of cement particles and subsequent production of small amounts of specific mediators. These mediators stimulate surrounding osteoblasts to secrete PGE2, which then amplifies the inflammatory response and ultimately results in bone resorption and aseptic loosening.

Arachidonic Acid↗

Effect of calcium citrate supplementation on urinary calcium oxalate saturation in female stone formers: implications for prevention of osteoporosis.

In 14 women aged 37-68 y with a history of renal calcium calculi, bone densities were 12.0% below those of age-matched control subjects at the L2-4 lumbar spine (P = 0.007) and 6.4% less at the femoral neck (P = 0.095). A low-oxalate diet was supplemented with 1 g Ca/d as citrate. In 6 mo, plasma 1,25(OH)2D concentrations fell from 53.2 +/- 18.8 to 41.9 +/- 15.2 ng/L (P = 0.02) and parathyroid hormone from 39.1 +/- 17.0 to 30.8 +/- 12.5 ng/L (P = 0.02). Calcium oxalate saturation was 2.15 +/- 1.38 at baseline, 2.27 +/- 1.00 at 1 mo, and 2.06 +/- 1.57 at 6 mo. The increase in urinary calcium at 1 mo from 4.411 +/- 1.87 to 6.514 +/- 2.82 mmol/24 h (P = 0.01) was offset by a parallel increase in citrate excretion from 2.909 +/- 1.45 to 3.455 +/- 1.34 mmol/24 h (P = 0.03). Calcium citrate supplementation did not increase the lithogenicity of the women in this protocol.

Adult↗

Allograft reconstruction after proximal tibial resection for bone tumors. An analysis of function and outcome comparing allograft and prosthetic reconstructions.

Seventeen patients (age, 12-63 years; median, 22 years) treated with proximal tibial allografts were identified. Nine cases were intercalary and eight were osteoarticular allografts. Complications, number of operations, and oncologic and functional results were reviewed. The functional results of the allografts were compared with a prior cohort of patients who had endoprosthesis at the same institution by the same surgeons. There were 14 malignant tumors, two benign aggressive tumors, and one sclerosing osteomyelitis mimicking osteosarcoma. Twelve of 17 patients had complications, the most common being fracture, deformity, and infection. Six patients required more than one procedure, and three had amputations after allograft reconstruction. The ultimate function was excellent in three patients, good in seven, fair in six, and poor in one. There were 14 patients with endoprosthetic reconstruction. Wound problems followed by prosthetic loosening were the most common complications. Of the eight patients requiring a second procedure, three had an amputation. Three had excellent, seven good, and four fair functional results at the final evaluation. No patient in either group had a local recurrence. Allograft provides an alternative to endoprosthetic reconstruction; however, the high incidence of complications makes the outcome unpredictable. Allograft or prosthetic reconstruction provides better functional results than amputation without sacrificing oncologic results.

Adolescent↗

Evaluation of bone-grafting materials in a new canine segmental spinal fusion model.

This paper describes a new canine segmental spinal fusion model for the comparison of bone-grafting materials. The test sites in the model are three separate posterior interfacet-interlaminar fusion sites in the lumbar spine (L1-2, L3-4, and L5-6). The outcome was assessed by scoring of the fusion sites for union and by mechanical testing of fused segments. The results from two experiments are presented. Autogenous cancellous bone was the most effective material tested and had a statistically superior score for union compared with all other materials (p = 0.01). The results with an osteoconductive matrix of collagen and ceramic alone were no better than those with the controls (no graft). However, addition of an extract of matrix-derived proteins (15-30 kDa) to the collagen-ceramic carrier appeared to improve the score for union. The inclusion of nonresorbed ceramic granules had no evident effect on the mechanical properties of fusions, with a comparable score for union. This model appears to be a sensitive and efficient method for the comparison of graft materials. Advantages over previously described models are discussed.

Animals↗

Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute.

The model of Norden was used to induce osteomyelitis in the left tibia of New Zealand White rabbits. Twenty-one days following inoculation, the animals had primary debridement and then were randomized into one of three treatment groups. Group I received no additional treatment; in Group II, plain hydroxyapatite beads were packed into the defect; and in Group III, gentamicin crobefat-loaded hydroxyapatite beads were packed into the defect. The animals were observed for 40 days after the primary debridement and then were killed. The intensity of infection was determined by swab cultures and quantitative bacterial cultures of the debrided material. At primary debridement, all of the animals in each group were equally infected. At the time of secondary debridement, only the animals in Group III had a statistically significant reduction in infection (p < 0.001). In this study, we demonstrated that an antibiotic-loaded osteoinductive ceramic bead can effectively eliminate bacteria from an osteomyelitic cavity.

Animals↗

A PCR-based linkage map of human chromosome 1.

A genetic linkage map of human chromosome 1 based entirely on PCR-typable markers has been developed using 38 simple sequence repeat (SSR) polymorphisms. These SSRs include 36 dinucleotide repeats and 2 tetranucleotide repeats. The average heterozygosity at these markers was 0.73 and ranged from 0.52 to 0.95. Multipoint linkage analysis was used to develop a map of these 38 markers in which the relative placement of each locus is supported by likelihood odds > 1000:1. This PCR-based map was anchored at the centromere by the D1Z5 alpha-satellite polymorphism, and the ends of the map were defined by D1Z2 and D1S68, which are the most distal loci in the CEPH consortium map of chromosome 1. The sex-averaged, male, and female maps extend for 328, 273, and 409 cM, respectively. The average distance between markers on the sex-averaged map is 8 cM, and the largest interval is 32 cM. This map of highly informative PCR-based markers will provide a rapid means of screening human chromosome 1 for the presence of disease genes.

Base Sequence↗

Measles vaccine efficacy study in a Canberra high school: a study following a measles outbreak.

An outbreak of measles which occurred in Canberra between October and December, 1991, was investigated to estimate the public health utility of the vaccine. The measles vaccine efficacy was determined for the 13-15 year old children in a selected high school. During the outbreak, at least 82 Canberra children contracted measles. Teenage males accounted for 56% of total cases, and 22% of cases were confirmed by serology. The vaccine coverage in the high school studied decreased with increasing school years, varying from 85.8% in Grade 8 to 79.2% in Grade 10. The highest attack rate occurred in Grade 10 (66/1000). The vaccine efficacy for age 13-15 was estimated to be 72% (95% Cl, 45-86%) but varied from 67 to 73%. Measles remains a serious disease of childhood in Australia. The elimination of measles is only partly dependent on the vaccine coverage of children. Issues relating to the effectiveness of vaccine are also important. A two dose vaccine strategy with the second dose of measles, mumps, rubella vaccine (MMR), given preferably in the last year of primary school or the first year of high school, is supported by the findings of this study.

Adolescent↗

Studies of the mechanism by which the mechanical failure of polymethylmethacrylate leads to bone resorption.

The purpose of this study was to examine the relationship between the mechanical failure of polymethylmethacrylate and bone resorption at the bone-cement interface of a prosthesis. Evaluation of tissue that had been retrieved from the cement-bone interface of eighteen femoral components of total hip prostheses that were loose without associated infection revealed that a critical factor associated with bone resorption was the presence of particles that were small enough (one to twelve micrometers) to be phagocytized by macrophages. To study this phenomenon in vitro, macrophages in tissue culture were exposed to three preparations of polymethylmethacrylate cement. A novel method of cement preparation was used with control for solid and soluble contaminants, which provided a sensitive and specific technique for the determination of which mediators were released from the macrophages. Electron microscopy demonstrated phagocytosis of particles of less than twelve micrometers in size, regardless of the type of cement preparation. Exposure to all three cement preparations resulted in toxicity, as reflected by inhibition of 3H-thymidine incorporation. Exposure also led to increased release of tumor necrosis factor, but none of the three preparations resulted in release of prostaglandin E2. Division of the cement preparations into two groups on the basis of the size of the particles demonstrated that exposure to particles that were small enough to be phagocytized led to inhibition of 3H-thymidine incorporation and release of tumor necrosis factor, while exposure to particles that were too large to be phagocytized did not. Neither exposure to small particles nor exposure to large particles of cement led to release of prostaglandin E2. Our results show that when the mechanical failure of cement produces particles that are small enough to be phagocytized, phagocytosis of the particles results in the increased production of tumor necrosis factor by the macrophages, which may in turn lead to bone resorption and prosthetic loosening. These small particles also decrease 3H-thymidine uptake by the macrophages.

Bone Cements↗