Biomedical subjects

Michael A Smith

Publications and source records attributed to Michael A Smith.

24 records · Page 2Linked to original sources

PubMed2002

Indirect recognition and antibody production against a single mismatched HLA-A2-transgenic molecule precede the development of obliterative airway disease in murine heterotopic tracheal allografts.

BACKGROUND: Previous studies have implicated the allogeneic immune response in the development of obliterative bronchiolitis after lung transplantation. However, the progression of specific pathogenic events leading to this form of chronic allograft dysfunction have not been well characterized. We used a murine tracheal transplantation model in which a single mismatched HLA-A2-transgenic molecule is indirectly recognized by the recipient CD4(+) T cells to show that obliterative airway disease (OAD) that developed in these allografts was preceded by indirect recognition of the HLA-A2 molecule and subsequent development of anti-HLA-A2 antibodies. METHODS: Tracheas from HLA-A2(+) C57BL/6 mice were heterotopically transplanted into C57BL/6 mice. Allograft histopathology as well as anti-HLA-A2 T-cell proliferative responses and anti-HLA-A2 antibody development were determined at days 5, 10, 20, and 28 after transplantation. RESULTS: All of the HLA-A2(+) tracheal allografts transplanted into C57BL/6 recipients demonstrated complete development of OAD by day 20. Spleen cells from the mice that underwent transplantation demonstrated significant proliferation against HLA-A2(+) cells by day 5. Indirect recognition of HLA-A2-derived peptides by spleen cells from allograft recipients was also higher on days 5 and 10 as compared with irrelevant peptides derived from HLA-A1, HLA-A3, and HLA-B44. Allograft recipients showed detectable levels of anti-HLA-A2 antibodies by day 5 and full development of anti-HLA-A2 antibodies by day 20. CONCLUSION: These results show that sensitization of CD4+ T cells against the mismatched HLA-A2 alloantigen precedes the development of anti-HLA antibodies as well as OAD, suggesting an important role for alloreactive CD4(+) T-cell activation and alloantibody development in the immunopathogenesis of OAD.

Animals↗

PubMed2002

Use of magnetic resonance angiography to select candidates with recently symptomatic carotid stenosis for surgery: systematic review.

OBJECTIVE: To determine if sufficient evidence exists to support the use of magnetic resonance angiography as a means of selecting patients with recently symptomatic high grade carotid stenosis for surgery. DESIGN: Systematic review of published research on the diagnostic performance of magnetic resonance angiography, 1990-9. MAIN OUTCOME MEASURES: Performance characteristics of diagnostic test. RESULTS: 126 potentially relevant articles were identified, but many articles failed to examine the performance of magnetic resonance angiography as a diagnostic test at the surgical decision thresholds used in major clinical trials on endarterectomy. 26 articles were included in a meta-analysis that showed a maximal joint sensitivity and specificity of 99% (95% confidence interval 98% to 100%) for identifying 70-99% stenosis and 90% (81% to 99%) for identifying 50-99% stenosis. Only four articles evaluated contrast enhanced magnetic resonance angiography. CONCLUSIONS: Magnetic resonance angiography is accurate for selecting patients for carotid endarterectomy at the surgical decision thresholds established in the major endarterectomy trials, but the evidence is not very robust because of the heterogeneity of the studies included. Research is needed to determine the diagnostic performance of the most recent developments in magnetic resonance angiography, including contrast enhanced techniques, as well as to assess the impact of magnetic resonance angiography on surgical decision making and outcomes.

Carotid Stenosis↗

PubMed2002

Rotational remapping in human spatial memory during eye and head motion.

The brain uses vision and other senses to compute the locations of objects relative to the body, and then must update these locations when the body moves. How geometrically sophisticated is this internal updating? It has been suggested that updating simply shifts the stored locations of all objects uniformly, by a common vector, when the eye or head turns. For horizontal and vertical turns, a uniform shift would often approximate the real changes in location of objects in front of the subject. But for torsional rotations, a shift would be inadequate: accurate updating would call for a more geometrically exact remapping, not shifting but rotating the stored locations through the inverse of the rotation of the eye in space. Here we asked human subjects to make eye saccades to remembered targets after torsional head rotations. Their accuracy showed that spatial updating works in the torsional dimension and operates by rotation rather than shifting.

Adult↗

PubMed2002

Soft tissue aneurysmal bone cyst: a clinicopathologic study of five cases.

We describe five primary soft tissue tumors that had histologic features identical to intraosseous aneurysmal bone cyst. The tumors occurred in three females and two males, who ranged in age from 8 to 37 years (median 28 years). They arose in the deep soft tissue of the upper extremities, thigh, and groin region and typically presented as a rapidly growing mass; no involvement of the adjacent bones was identified. The tumors ranged in size from 2.5 to 9 cm (median 4 cm). Grossly, they were surrounded by a thin rim of bone and on sectioning had hemorrhagic cystic spaces delineated by fibrous septa. Histologically, the cystic spaces were filled with blood and the fibrous septa were composed of fibroblasts, osteoclast-type giant cells, and woven bone. Cytogenetic analysis of one tumor showed 46,XY,t(17;17)(p13;q12), a result similar to that which has been reported for intraosseous aneurysmal bone cyst. The differential diagnosis includes a variety of bone-forming and giant cell-containing tumors, the most important being extraskeletal osteosarcoma. Follow-up showed that four patients are free of disease 16 months to 10 years after surgery; one tumor regrew after incomplete initial excision, but the patient has been free of disease 16 months after a second operation. Soft tissue aneurysmal bone cyst is an uncommon benign tumor that can be treated by simple excision, and it should be distinguished from a variety of other reactive and neoplastic processes.

Adolescent↗

PubMed2002

How to undertake a clinically relevant systematic review in a rapidly evolving field. Magnetic resonance angiography.

OBJECTIVES: The aim was to determine which generations of the evolving technology of magnetic resonance angiography (MRA) are currently of clinical relevance in two clinical applications. Our purpose was to plan a systematic review that would be valuable both to purchasers driven by cost-effectiveness and to practicing clinicians. METHODS: Information was gathered from a search of major bibliographic databases, from a short questionnaire sent to 500 U.K. vascular radiologists and vascular surgeons, and from local clinical experts. We asked which of the MRA techniques were currently used and, assuming availability, what would be their technique of choice. RESULTS: There were 206 published articles that satisfied preliminary inclusion criteria: 69 discussed 2D time of flight (TOF); 47, 3D TOF; and 38, contrast-enhanced techniques. There were 162 questionnaires returned (60 radiologists, 102 surgeons). Of the total respondents, 77/162 (48%) used MRA in the assessment of carotid artery stenosis; 47/77 (61%) used 2D TOF; 32/77 (42%), 3D TOF; and 26/77 (34%), contrast-enhanced techniques. Thirty-five of 162 (22%) respondents used MRA in the assessment of peripheral vascular disease (PVD); 15/35 (43%) used 2D TOF, 4/35 (11%) used 3D TOF, and 22/35 (63%) used contrast-enhanced techniques. For those wishing to use MRA, contrast-enhanced techniques were the method of choice. CONCLUSIONS: The TOF methods that represent earlier generations of the technology remain clinically relevant, and will therefore be included in our systematic review. To ensure complete and relevant coverage in reviews of other evolving technologies, it would be advisable to obtain data for guidance in a similar way.

Humans↗

PubMedDate not supplied

Abnormalities of body composition in peritoneal dialysis patients.

OBJECTIVES: Body composition changes occur in peritoneal dialysis (PD) due to abnormalities in nutrition and hydration. We investigated abnormalities of nutrition and hydration in PD patients compared with healthy controls by measurement of total body potassium (TBK) and body water compartments. DESIGN: Cross-sectional comparison study. METHODS: We measured TBK--an indicator of body cell mass--by whole body counting, total body water (TBW) by deuterium oxide dilution, and extracellular water (ECW) by bromide dilution in 29 PD patients and 32 controls. RESULTS: The absolute mean value of TBK for PD patients was not significantly lower than in controls. The ratios of observed TBK to predicted TBK from prediction formulas were compared. Equations used were those of Boddy, Bruce, Burkinshaw, and Ellis and our own equation derived from a local control database (Leeds). Observed/predicted ratios of TBK were significantly less in PD than in control subjects for all equations. Water volumes did not differ between PD and control groups. Observed/predicted ratios for TBK in PD patients correlated with serum potassium (Boddy r = 0.355, p = 0.06; Bruce r = 0.411, p < 0.05; Burkinshaw r = 0.457, p < 0.01; Leeds r = 0.412, p < or = 0.05; Ellis r = 0.356, p = 0.06) and tended to correlate with serum albumin (Bruce r = 0.343, p = 0.07; Burkinshaw r = 0.421, p < 0.05; Leeds r = 0.357, p = 0.06; Ellis r = 0.310, p = NS). There was no relationship with serum potassium in controls. Serum albumin in PD correlated with TBK (r = 0.445, p < 0.02), TBK/height (r = 0.419, p < 0.05), TBK/weight (r = 0.554, p = 0.002), and TBK/TBW (r = 0.586, p = 0.0001). Extracellular water/intracellular water (ECW/ICW) was inversely related to TBK (r = -0.455, p < 0.02 in PD; r = -0.387, p < 0.05 in controls) and to TBK/height (r = -0.446, p < 0.02 in PD; r = -0.411, p = 0.02 in controls). TBK/weight reduced with age in PD (r = -0.445, p < 0.02), as did TBK/TBW in PD (r = -0.463, p < 0.02). ECW/ICW tended to increase with age in PD (r = 0.351, p = 0.06). CONCLUSIONS: Observed/predicted ratio of TBK is reduced in PD patients relative to healthy controls, indicating reduced body cell mass. Serum albumin and potassium reflect TBK indices in PD. Body water volumes did not differ between PD and controls, implying no overall abnormality in hydration in the PD group. However, ECW is relatively increased compared to ICW with decreasing TBK indices, suggesting relative ECW expansion with reduction in body cell mass.

Adult↗