Wise withdrawal?
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Biomedical subjects
Publications and source records attributed to G J Marshall.
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The Antarctic contribution to sea-level rise has long been uncertain. While regional variability in ice dynamics has been revealed, a picture of mass changes throughout the continental ice sheet is lacking. Here, we use satellite radar altimetry to measure the elevation change of 72% of the grounded ice sheet during the period 1992-2003. Depending on the density of the snow giving rise to the observed elevation fluctuations, the ice sheet mass trend falls in the range -5-+85Gtyr-1. We find that data from climate model reanalyses are not able to characterise the contemporary snowfall fluctuation with useful accuracy and our best estimate of the overall mass trend-growth of 27+/-29Gtyr-1-is based on an assessment of the expected snowfall variability. Mass gains from accumulating snow, particularly on the Antarctic Peninsula and within East Antarctica, exceed the ice dynamic mass loss from West Antarctica. The result exacerbates the difficulty of explaining twentieth century sea-level rise.
We report an undocumented major warming of the Antarctic winter troposphere that is larger than any previously identified regional tropospheric warming on Earth. This result has come to light through an analysis of recently digitized and rigorously quality controlled Antarctic radiosonde observations. The data show that regional midtropospheric temperatures have increased at a statistically significant rate of 0.5 degrees to 0.7 degrees Celsius per decade over the past 30 years. Analysis of the time series of radiosonde temperatures indicates that the data are temporally homogeneous. The available data do not allow us to unambiguously assign a cause to the tropospheric warming at this stage.
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Periodontitis is a chronic bacterial infection of the supporting structures of the teeth. The host response to infection is an important factor in determining the extent and severity of periodontal disease. Systemic factors modify periodontitis principally through their effects on the normal immune and inflammatory mechanisms. Several conditions may give rise to an increased prevalence, incidence or severity of gingivitis and periodontitis. The effects of a significant number of systemic diseases upon periodontitis are unclear and often it is difficult to causally link such diseases to periodontitis. In many cases the literature is insufficient to make definite statements on links between certain systemic factors and periodontitis and for several conditions only case reports exist whereas in other areas an extensive literature is present. A reduction in number or function of polymorphonuclear leukocytes (PMNs) can result in an increased rate and severity of periodontal destruction. Medications such as phenytoin, nifedipine, and cyclosporin predispose to gingival overgrowth in response to plaque and changes in hormone levels may increase severity of plaque-induced gingival inflammation. Immuno-suppressive drug therapy and any disease resulting in suppression of the normal inflammatory and immune mechanisms (such as HIV infection) may predispose the individual to periodontal destruction. There is convincing evidence that smoking has a detrimental effect on periodontal health. The histiocytoses diseases may present as necrotizing ulcerative periodontitis and numerous genetic polymorphisms relevant to inflammatory and immune processes are being evaluated as modifying factors in periodontal disease. Periodontitis severity and prevalence are increased in diabetics and worse in poorly controlled diabetics. Periodontitis may exacerbate diabetes by decreasing glycaemic control. This indicates a degree of synergism between the two diseases. The relative risk of cardiovascular disease is doubled in subjects with periodontal disease. Periodontal and cardiovascular disease share many common risk and socio-economic factors, particularly smoking, which is a powerful risk factor for both diseases. The actual underlying aetiology of both diseases is complex as are the potential mechanisms whereby the diseases may be causally linked. It is thought that the chronic inflammatory and microbial burden in periodontal disease may predispose to cardiovascular disease in ways proposed for other infections such as with Chlamydia pneumoniae. To move from the current association status of both diseases to causality requires much additional evidence. Determining the role a systemic disease plays in the pathogenesis of periodontal disease is very difficult as several obstacles affect the design of the necessary studies. Control groups need to be carefully matched in respect of age, gender, oral hygiene and socio-economic status. Many studies, particularly before the aetiological importance of dental plaque was recognised, failed to include such controls. Longitudinal studies spanning several years are preferable in individuals both with and without systemic disease, due to the time period in which periodontitis will develop.
The effectiveness of methotrexate eluted from polymethylmethacrylate on cell lines established from giant cell tumor of bone was investigated in vitro to determine the possible efficacy of this treatment. Elation of methotrexate from polymethylmethacrylate beads and boluses was shown in vitro to be dose dependent and limited by the size of the bolus. Cytocidal activity of methotrexate elated from polymethylmethacrylate beads prepared without monomer and of boluses of polymethylmethacrylate with the same dose of methotrexate prepared with monomer against 2 human giant cell tumor cell lines was statistically significant at 24 hours in culture. Statistical significance occurred at 24 hours in culture. Activity was maintained in vitro after 17 days. These experiments showed that eluted methotrexate remained effective against tumor cells after exposure to thermal changes during polymerization of polymethylmethacrylate. While extensive curettage of giant cell tumor of bone followed by filling in the defect with polymethylmethacrylate has become a common treatment, a local adjuvant is necessary to reduce further risk of local recurrence. A potential alternative to cryosurgery or instillation of phenol is the use of methotrexate impregnated polymethylmethacrylate to treat residual microscopic disease after curettage. This method may provide locally effective chemotherapy without the risks of systemic toxicities.
STUDY DESIGN: In this study, 10 patients with chronic irreducible atlantoaxial dislocation were treated by transoral anterior decompression and fusion. OBJECTIVES: To examine the benefits of the transoral approach, the patients treated with this procedure were compared with the historical control subjects after 2 years of follow-up. SUMMARY AND BACKGROUND DATA: Chronic irreducible atlantoaxial dislocation with cord compression is difficult to treat because the cord is compressed posteriorly by the posterior arch of the atlas as well as anteriorly by the posterior-superior portion of the axial body and nonunited dens. Its irreducibility, as a result of the bony scarring between the dens and the anterior body of the axis, and the locking of the lateral joints of C1-C2, makes reduction more complex. Posterior surgical approaches have been associated with high morbidity and mortality. METHODS: Ten patients were diagnosed and followed up by clinical symptoms, radiography, pantopaque myelography, and computed tomography. They were treated surgically by transoral decompression and fusion. During the surgery the nonunited dens as well as callus, granulation, and scar tissue were removed; the cartilage of the articular surfaces of the atlantoaxial joint was excised. Postoperative treatment included skull-cervical biaxial traction, tracheostomy care, nasal feeding, and Minerva cast. RESULTS: The 2- to 6-year follow-up showed that four out of 10 patients recovered completely and returned to work, three recovered to a great degree and ambulated, two partially recovered, and one recovered poorly. CONCLUSION: Transoral decompression and fusion offered satisfactory results in a series of patients with chronic irreducible atlantoaxial dislocation. None of the patients showed serious complications of stability, even though only one had a secondary posterior fusion. Therefore, anterior decompression associated with subtotal obliteration of the atlantoaxial joints without bone grafts is a feasible therapy for irreducible atlantoaxial dislocation using a multifunctional bed and biaxial traction.
Partial meniscectomies were performed on 32 fresh human meniscal autopsy specimens. The following laser systems were tested: carbon dioxide (CO2), neodymium:yttrium aluminum garnet (Nd:YAG), potassium titanyl phosphate (KTP), holmium:YAG (Ho:YAG), and excimer. Meniscectomies with these lasers were compared with scalpel, mechanical, and electrocautery meniscectomies. Lasers were applied to specimens in and out of normal saline. Routine hematoxylin and eosin and sirius red sections were prepared for each specimen, and the depths of thermal changes were analyzed. Scanning electron microscopy was used to visualize the meniscectomy interface. Among these specimens, the scalpel and mechanical meniscectomies showed the least extension of cellular changes (range, 10-15 nm). The excimer laser caused the least tissue changes of the lasers tested. Tissue changes were less extensive with the pulsed CO2 laser than with the holmium:YAG, neodymium:YAG, and KTP lasers. Scanning electron microscopy showed that use of the scalpel meniscectomy resulted in the smoothest meniscectomy edge, followed by use of the excimer, CO2, holmium:YAG, neodymium:YAG, and KTP lasers. The most surface disruption occurred with electrocautery. Meniscectomies under saline required more energy and took longer in each case, with the holmium:YAG, neodymium:YAG, and CO2 laser cutting the best. Saline meniscectomies showed less thermal change. The CO2 and KTP lasers cut best in air.
A pulsed carbon dioxide laser made predetermined superficial and deep (subchondral) lesions through arthrotomies on the femoral condyles of adult New Zealand rabbits. Twenty rabbits, including controls, were divided into acute, 1-, 3-, 6-, and 12-month sacrifice groups. Early sacrifice groups showed some fibrous ingrowth from the deep lesions, but not the superficial lesions, and this was not seen in the 6- or 12-month groups. Cells below and adjacent to the laser lesions appeared viable when compared with controls. In each group studied, no histologic evidence of healing or fibrous covering in the superficial or deep laser lesions was found. No adverse clinical effects (synovitis, infection) were found in the laser groups, and the laser permitted excellent depth control during vaporization. However, the authors caution against irradiating articular cartilage.
Bone healing was investigated histologically in a rat fibular osteotomy model subjected to microgravity (shuttle flight STS-29) and the tail suspension microgravity simulation model. Exposure to microgravity or tail suspension occurred during the last 5 days of a 10-day healing period. Periosteal osteogenesis and the development of vascular channels in both experimental groups were similar to that observed in a weightbearing control group. Chondrogenesis was more advanced in weightbearing rats than in either flight or tail-suspended rats. Angiogenesis in the osteotomy gap was more advanced in weightbearing and tail-suspended rats than in the flight group. These findings suggest that bone healing may be impaired during space travel. Interpretation of the findings is complicated by observations that flight and suspended rats lost weight during the flight period and that suspended rats consumed less water than control rats. Tail suspension did not produce the same pattern of healing as spaceflight; therefore, long-term studies of bone healing, conducted entirely in the microgravity environment, are needed to distinguish metabolic from mechanical influences and to determine whether effective fracture consolidation will occur in the absence of gravitational forces.
Thirty mature New Zealand white rabbits were divided into four surgical groups, and a 3- to 4-mm incision was made in the inner avascular zone of the central third of the medial meniscus. In group I, the tear was not treated by lasering or suturing. In group II, the tear was sutured. Group III was given four different doses of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation with no suturing. Group IV underwent meniscal suturing followed by the same four different laser irradiation doses. The animals were killed at 2, 4, and 6 weeks, with gross and histologic evaluation of the healing responses by group and time. The overall results showed no healing of this meniscal tear in the avascular zone. Suturing generally showed increased cellular infiltration. The varying doses of the Nd:YAG lasing demonstrated no gradient effect, and no "welding" of menisci was noted. The maximum cellular inflammatory response was noted in the sutured and lased menisci, reinforcing the importance of a stable meniscal environment for healing meniscal tears.
Storage of lymphocytes for later use in prospective epidemiologic studies of blood donors and transfusion recipients has been limited by the cost of separating peripheral blood mononuclear cells (PBMCs). When the Transfusion Safety Study began in 1985, it was decided to establish a cell repository of cryopreserved buffy coat (BC) samples, and thus far over 20,000 samples have been accumulated from enrolled subjects. To determine if these specimens could be used for polymerase chain reaction, a simple thawing and pelleting technique for recovering hemoglobin-free total white cells (WBCs) was developed. To validate the technique, parallel analysis was conducted of BCs, whole blood (WB), and PBMC samples from human immunodeficiency virus type 1 (HIV-1)-seropositive subjects. Immediate postthaw cell courts of 29 frozen-thawed (F-T) WB and BC samples averaged 90 percent of the prefreeze (input) values. Representative WBC populations were obtained by immediate pelleting. Amplification of HIV-1 gag sequences from F-T BCs and F-T WB was 94 and 75 percent, respectively, which is as sensitive as that obtained with freshly separated PBMC lysates. Quantitative HIV-1 proviral load analysis by serial dilution of 23 F-T BCs and 8 WB lysates showed results comparable to those obtained with lysates of fresh PBMCs. Values for WBC differential and immunophenotyping could be applied to express viral load relative to total WBCs, PBMCs, or CD4+ cells. These results establish the basis for simplified virologic analysis of cryopreserved BC or WB specimens.
Accurate knowledge of tissue changes near bone tumors can contribute to a better understanding of tumor behavior. We have used tumor ultrastructure and quantitative bone histomorphometry to evaluate local bone/tumor features associated with a low grade chondrosarcoma in a 39-year-old male. Three noninvolved sites and two sites near the tumor in the proximal femur were studied with bone morphometry. Bone near the tumor showed increased percent osteoid surface, percent osteoid volume and fraction of osteoid surface lined by osteoblasts compared to distant noninvolved sites. Both the number of osteoblasts and mean individual osteoblast size were significantly increased compared to noninvolved sites. Osteoclast number and percent osteoclast surface were also increased near the tumor. Ultrastructural studies of tumor tissue revealed two types of tissue: synthetic mesenchymal cells and cartilage tissue. Results indicate increased bone formation and resorption near the tumor. These local bone changes may possibly reflect responses to local tumor factors and depend on the extent of the tumor.
Healing of 0.5 or 1.0-millimeter step-off defects associated with displaced intra-articular fractures of the medial femoral condyle was examined in fifty-four adult New Zealand White rabbits. The rabbits were treated with either immobilization for three weeks, intermittent active motion, or continuous passive motion for seven days. At twelve weeks, the healing and remodeling of the step-off defects were examined with use of contact-pressure maps on pressure-sensitive film, light microscopy (with hematoxylin and eosin or safranin-O staining), and scanning electron microscopy. Macroscopically, the sharp profile that had been present initially with both sizes of step-off defect had rounded off; however, there was less residual incongruity with the 0.5-millimeter step-offs than with the 1.0-millimeter step-offs. Among step-off defects of the same size, the method of treatment had no discernible effect on the macroscopic appearance of the surface of the joint. With fresh step-offs (the control group), the contact pressure of the cartilage on the elevated side was approximately three times greater than that at a distance from the step-off. On the depressed side, an unloaded zone extended approximately three times the height of the step-off, with an average width of 3.4 millimeters for the 1.0-millimeter step-offs and 1.6 millimeters for the 0.5-millimeter step-offs. After healing and remodeling, the unloaded zone still averaged 2.5 millimeters in width for the 1.0-millimeter step-offs but had decreased to only 0.35 millimeter in width for the 0.5-millimeter step-offs. For seven of the nine 0.5-millimeter step-offs, the contact pressure in the previously unloaded zone ranged from 0.5 to 1.5 megapascals, with a mean of 0.8 megapascal (40 per cent of the normal mean contact pressure at this location). Under light microscopy, the cartilage on the elevated side of the healed step-offs had decreased in thickness, was displaced toward the defect and tapered toward the depressed side, and ended in a hypocellular tissue flap. In contrast, the cartilage on the depressed side had thickened as a result of hyperplasia of the chondrocytes and hypertrophy of the cartilage and had failed to establish continuity between the sides of the defect. There was a marked increase in the subchondral vascular bed and re-establishment of the subchondral plate. With the exception of the aforementioned hypocellular tissue flap, safranin O stained the cartilage on both levels of the step-off uniformly, which indicated the absence of glycosaminoglycan depletion.(ABSTRACT TRUNCATED AT 400 WORDS)
Giant cell tumors of bone are common but unusual tumors that are comprised of multiple cell types. Most attention has been focused on the giant cells, which resemble osteoclasts morphologically and functionally. This study examines the properties of a cell line derived from mononuclear cells from one of these tumors, since it appears likely that these cells may be able to influence the activities of cells with the osteoclast phenotype. This cell line, C433, has the following characteristics: (1) it represents undifferentiated cells, not recognized by any known antigenic markers for leukocytes; (2) it contains tartrate-resistant acid phosphatase; (3) it responds to the osteotropic factors 1,25 dihydroxyvitamin D3, insulin-like growth factor I and II, but not to parathyroid hormone; (4) it forms sarcomas in nude mice; and (5) it produces an activity that stimulates isolated avian and rat osteoclasts to resorb bone. This cell line may be useful in examining interactions between osteoclasts and accessory cells involved in bone resorption.
The healing of freeze-dried, ethylene oxide sterilized, segmental, allogenic cortical bone grafts was investigated in 15 rabbits using a 2-cm ulnar diaphyseal defect. Five different groups of bone grafts were evaluated: 1) unperforated undemineralized, 2) perforated undemineralized, 3) unperforated demineralized, 4) perforated demineralized, and 5) perforated demineralized grafts enclosed by silicone rubber (Silastic) sheets. There were 3 animals in each group. At 18 days, the study was terminated, and the implants were examined using radiographs and qualitative histologic preparations. We observed that healing of perforated demineralized bone was superior to unperforated demineralized bone, that undemineralized bone was partially sequestered in reactive lacunae, and that perforations in demineralized bone became centers of osteoinduction. Demineralized bone sterilized with ethylene oxide by this method vigorously formed new bone.
Two case studies are presented in which quantitative bone histomorphometry is used to analyze bone changes in adult patients with diagnosed spindle cell sarcoma. Three tumor-involved sites and one noninvolved site from the iliac crest of patient 1 were evaluated. In the involved sites the percentage trabecular bone volume (11.0%) and the number of osteoblasts (0.6 cell/mm2) were significantly reduced, osteoid volume was significantly increased (8.1%), and woven osteoid was present. The total eroded surface (6.8%) was also significantly increased. In the noninvolved site the number of osteoblasts was decreased and both the percentage eroded and percentage osteoclast surfaces were increased. In the femoral epicondyle specimen from patient 2 the number of osteoblasts was 27.0 cells/mm2, percentage osteoid volume was 18.4%, percentage osteoid surface was 62.9%, and osteoid thickness was 20.0 microns. In tumor-involved sites in both patients indices of active bone resorption were similar and normal. These two case studies indicate that (1) distinctive morphologic changes occur in bone invaded by spindle cell sarcoma, and that (2) changes affect bone formation to a greater extent than bone resorption. Bone alterations are probably local in nature and related to the extent and duration of tumor invasion and the influence of local tumor factor(s).
The Transfusion Safety Study (TSS) and the National Heart, Lung, and Blood Institute (NHLBI) established a repository of approximately 200,000 sera from blood donors in late 1984 and early 1985. Collections were made in the four metropolitan areas with the highest prevalence of AIDS. Retrospective testing showed an overall anti-HIV-1 prevalence of 16 cases per 10,000 donations. In this study, the predictive value of a negative initial enzyme-linked immunoassay was estimated from both quality control specimens and the rescreening of 13,461 sera to be greater than 99.99 percent with respect to technical error. Among anti-HIV-1-positive persons, there was a 1.3- to 1.5-fold excess of first-time donors. The anti-HIV-1 prevalence among donors showed that infection was more common among young men than suggested by national reporting of AIDS cases. Anti-HIV-1 prevalence varied among the four metropolitan areas less than did reported AIDS cases, but, by 1987, the differences in the latter had decreased. Anti-HIV-1 prevalence in collection areas outside of the four major cities differed much more widely than that among the cities themselves. The TSS/NHLBI Donor Repository will remain available for the indefinite future for further evaluation of screening procedures for HIV-1 and other viruses for which transfusion is found to be an important route of transmission.