Search PubMed⌕ Search

Biomedical subjects

R M Smith

Publications and source records attributed to R M Smith.

At least 109 records · Page 6Linked to original sources
PubMed1999

Monocyte human leukocyte antigen-DR expression correlates with intrapulmonary shunting after major trauma.

BACKGROUND: Severe injury is often complicated by the development of sepsis and the adult respiratory distress syndrome. Since the outcome from severe injury also correlates with changes in monocyte human leukocyte antigen (HLA)-DR expression in such patients, the present study aimed to determine whether or not there was a relationship between monocyte HLA-DR expression and indicators of early pulmonary dysfunction. METHODS: Monocyte HLA-DR expression and serum interleukin (IL)-6 were measured on admission and then again on days 1, 3, 5, and 7 after major injury in 29 patients admitted for the management of trauma with an injury severity score of 9 or more. Noninvasive intrapulmonary shunt measurement was also performed in all these patients within 6 hours of emergency surgery in all patients. RESULTS: Monocyte HLA-DR followed the characteristic suppression followed by recovery in those who followed an uncomplicated course but progressively declined in those who suffered septic complications. The degree of intrapulmonary shunting observed 6 hours after injury in the patients who developed sepsis was significantly higher than that in the uncomplicated group. Peak monocyte HLA-DR expression during the recovery phase correlated inversely with the degree of intrapulmonary shunting. CONCLUSIONS: The degree of intrapulmonary shunting observed following severe trauma correlates with the failure of circulating monocytes to re-express HLA-DR antigen, and this may provide some insights into the early events that result in the adult respiratory distress syndrome after major injury.

Adult↗
PubMed1999

Postural control during stance in paraplegia: effects of medially linked versus unlinked knee-ankle-foot orthoses.

OBJECTIVE: To investigate the effect of medially linking knee-ankle-foot orthoses (KAFOs) on postural stability and sway during (1) quiet standing and (2) functional activities for persons with spinal cord injury (SCI). DESIGN: A randomized, mixed design, with the factors being activity (quiet standing and two function-mimicking tasks), SCI (present or not), and type of orthosis used in SCI group (linked or unlinked KAFO). PARTICIPANTS: Nine men with T5 to T12 paraplegia, 8 of whom had complete lesions and 1 with some sacral sparing (American Spinal Injury Association grade B) without proprioception, matched to 9 able-bodied men. MAIN OUTCOME MEASURES: Mean amplitude of sway and sway path in anteroposterior and mediolateral directions, derived from center of pressure measurements on a force platform. RESULTS: All men with SCI were able to stand unsupported and perform function-mimicking activities in medially linked KAFOs; however, when wearing unlinked KAFOs only 5 could maintain balance during quiet stance and 3 could maintain balance during activity. Significant differences were found between linked and unlinked KAFOs; side-to-side mean amplitude of sway was less and sway path was greater for SCI subjects when they wore the linked KAFOs. CONCLUSION: Medial linkage of bilateral KAFOs provides an effective strategy to improve stability and increase postural control for persons with SCI, facilitating performance of functional activities during standing without upper limb support.

Activities of Daily Living↗
PubMed1999

Exchange nailing for femoral shaft aseptic non-union.

Although rare, non-union of femoral shaft fractures is a cause of significant morbidity. In aseptic non-union, excellent union rates have historically been reported following reamed exchange femoral nailing. However, recently, a high incidence of failure requiring additional procedures has been reported. In light of these concerns and a recent change in our practice to the use of thin solid nails we undertook a retrospective study to determine the efficacy of exchange nailing with these modern nails in our hands. We reviewed records and radiographs of 25 patients who had a reamed exchange femoral nailing for established aseptic non-union. 24 patients (96%) united after exchange without the need for an additional procedure. The mean time to union was 29.75 weeks. Patients who had open bone grafting performed at the same procedure tended to unite quicker, but this did not achieve statistical significance (p = 0.14). Union times were not affected by smoking habits or nail type. This study demonstrates that reamed exchange nailing for aseptic femoral non-union remains an effective treatment. We believe that the nail type is less important than the biological effects of reaming, bone grafting and dynamization.

Adolescent↗
PubMed1999

Hepatocyte-directed gene delivery by receptor-mediated endocytosis.

The application of gene therapy to liver disease is contingent on the development of an effective gene delivery vehicle. Receptor-mediated endocytosis can be exploited as a means of selective and efficient targeting of gene therapy vectors to hepatocytes. DNA-binding conjugates have been directed to the liver by the attachment of asialoglycoproteins or other ligands for receptors expressed on hepatocytes. Recent studies suggest refinements in this approach through which high transduction rates in vitro may be reproduced in vivo. The intrinsic liver tropism of viral vectors and liposomes can be augmented by the addition of targeting features, as demonstrated in animal models. With further modification, such as the incorporation of hepatotropic elements of the hepatitis viruses or lipoproteins, the next generation of delivery systems may achieve efficient, persistent expression of therapeutic genes in a safe and cell type-specific manner.

Animals↗
PubMed1999

A rare fracture-dislocation of the hip in a gymnast and review of the literature.

Posterior fracture-dislocation of the hip is an uncommon injury in athletics and leisure activities. It is more commonly seen in high energy motor vehicle accidents and occasionally in high energy sporting activities. A rare case is reported of posterior fracture-dislocation of the hip joint that occurred in a young athlete during gymnastics. This unusual mechanism of injury illustrates the great forces sustained by the hip joint of gymnasts. Early reduction and operative treatment led to a congruent and stable hip joint. After rehabilitation, she returned to light sporting activities after six months.

Acetabulum↗
PubMed1999

Bronchopulmonary segmental lavage with Surfaxin (KL(4)-surfactant) for acute respiratory distress syndrome.

We performed a trial to assess the safety and tolerability of sequential bronchopulmonary segmental lavage with a dilute synthetic surfactant (Surfaxin) in 12 adults with ARDS. Patients received one of three dosing regimens in which aliquots of Surfaxin were administered via a wedged bronchoscope to each of the 19 bronchopulmonary segments. Suctioning was performed 10-30 s after instillation of individual aliquots. Group 1 patients (n = 3) received one 30-ml aliquot of a 2.5-mg/ml concentration of Surfaxin in each segment, followed by a second 30-ml aliquot with a 10-mg/ml concentration. Group 2 patients (n = 4) received two 30-ml aliquots of the 2.5-mg/ml concentration followed by a third lavage with the 10-mg/ml concentration. Group 3 patients (n = 5) received therapy identical to that received by patients in Group 2 and were eligible for repeat dosing 6 to 24 h later. All patients tolerated the procedure. There were no serious adverse experiences ascribed to either the procedure or the surfactant. In the 96 h after treatment initiation, FI(O(2)) decreased from 0.80 to 0.52 and PEEP decreased from 10.3 to 7.6 cm H(2)O. Bronchoscopic "cleansing" of the lungs with dilute Surfaxin may offer a safe and feasible approach to improving outcomes in patients with ARDS. Wiswell TE, Smith RM, Katz LB, Mastroianni L, Wong DY, Willms D, Heard S, Wilson M, Hite RD, Anzueto A, Revak SD, Cochrane CG. Bronchopulmonary segmental lavage with Surfaxin (KL(4)-surfactant) for acute respiratory distress syndrome.

Bronchoalveolar Lavage↗
PubMed1999

Stimulation of the inflammatory system by reamed and unreamed nailing of femoral fractures. An analysis of the second hit.

It has been suggested that reamed intramedullary nailing of the femur should be avoided in some patients with multiple injuries. We have studied prospectively the effect of femoral reaming on the inflammatory process as implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF). We studied changes in the levels of serum interleukin-6 (IL-6) (proinflammatory cytokine), neutrophil CD11b (C3) receptor expression (activated neutrophil adhesion molecule), serum soluble intracellular adhesion molecule (s-ICAM-1), serum soluble E-selectin (the soluble products of endothelial adhesion molecules) and plasma elastase (neutrophil protease) in a series of patients with femoral fractures treated by nailing. We have also compared reamed nailing with unreamed nailing. We found that the levels of serum IL-6 and elastase rose significantly during the nailing procedure indicating a measurable 'second hit'. There was no clear response in leukocyte activation and no difference in the release of endothelial adhesion molecule markers. There was no significant difference between groups treated by reamed and unreamed nailing. Although clinically unremarkable, the one patient who died from ARDS was shown to be hyperstimulated after injury and again after nailing, suggesting the importance of an excessive inflammatory reaction in the pathogenesis of these serious problems. Our findings have shown that there is a second hit associated with femoral nailing and suggest that the degree of the inflammatory reaction may be important in the pathogenesis of ARDS and MOF.

Adolescent↗
PubMed1999

Unreamed intramedullary nailing for pathological femoral fractures. Good results in 30 cases.

We have used the AO unreamed femoral nail for stabilization of impending and complete pathological fractures since March 1994. 27 patients with 30 pathological fractures (23) or impending fractures (7) of the femur were retrospectively analyzed. These included 18 subtrochanteric fractures, 11 shaft fractures and 1 distal fracture. The mean age of the patients was 68 (51-84) years. All patients were treated with a solid femoral nail inserted by an unreamed technique. The nail was inserted through a minimally invasive approach and with a median surgical time of 55 (35-70) minutes. A reconstructive proximal locking option (spiral blade) was used in 25 cases. There were no intraoperative complications, no operative mortality. Reliable skeletal stability was obtained in all cases and most were able to mobilize early with minimum discomfort. 1 case was revised for a secondary fracture through a distal metastasis at 6 months. The median survival was 5 (2-9) months. Unreamed nailing with the AO solid femoral nail appears to be a good option for the stabilization of pathological femoral fractures.

Aged↗
PubMed1999

Developing a unidimensional instrument to measure the effectiveness of school-based partnerships.

The purpose of this study was to refine an instrument designed to measure a single construct, the effectiveness of school-based partnerships. The instrument was designed to measure the "health" of the partnership teams and to identify specific problems for which intervention might be appropriate. The items were based on four theoretical models of partnering efforts. The partnerships studied were created to enhance the teaching of elementary school science and involved elementary teachers and resource professionals in school-based programs over a six-year period. The results show how Rasch analysis, using the item and person fit statistics, bias analysis using separate calibration groups for contrasts of interest, and principal component analysis can be used to evaluate the unidimensionality of a scale.

Community Participation↗
PubMed1998

Insulin-induced protein tyrosine phosphorylation cascade and signalling molecules are localized in a caveolin-enriched cell membrane domain.

The cellular localisation of time- and temperature-dependent 125I-insulin binding, insulin-sensitive signalling proteins and the insulin-induced protein tyrosine phosphorylation cascade were assessed in subcellular fractions isolated on Iodixanol gradients from control and insulin-treated H35 hepatoma cells. Western blot analysis demonstrated that the concentrations of IRS-1, Shc, GRB-2, SOS, Syp, PI 3-kinase, MAP kinase and Gi alpha were at least 10-fold higher in cell surface-derived, caveolin-enriched fraction than in a cell surface-derived, caveolin-poor fraction (i.e., the plasma membranes). Insulin treatment caused a 15-fold increase in tyrosine phosphorylation of IRS-1 in the caveolin-enriched fraction in 5 min at 37 degrees C compared with a 3-fold increase in plasma membranes and a 6-fold increases in the cytosol and endosomes. Insulin also increased tyrosine phosphorylation of both a 72-kDa protein and the 46-kDa Shc isoform only in the caveolin-enriched fraction. Insulin treatment did not change the concentrations of insulin receptors or Shc but increased IRS-1 in the caveolin-enriched fraction, possibly recruited from the cytosolic pool. Insulin also increased the concentrations of insulin receptors, IRS-1 and Shc in endosomes, suggesting insulin-induced internalization of the insulin receptors and proteins activated with them. Electron microscopic analysis, with the use of a combination of colloidal gold-labelled insulin to label the insulin receptor and immunolabelling to detect caveolin or IRS-1, demonstrated the co-localisation of insulin receptors in caveolin- and IRS-1 containing vesicular structures. Differences in the insulin-induced protein tyrosine phosphorylation and concentrations of these proximal signalling proteins in the caveolin-enriched fraction, plasma membranes, and cytosol suggest that insulin receptors in the caveolae play a major role in initiating insulin's signal transduction processes.

Binding Sites↗
PubMed1998

Stimulation of inflammatory markers after blunt trauma.

BACKGROUND: Inflammatory mediators are released after trauma and may be related to the pathogenesis of sepsis. A prospective combined study of the pattern of release of an inflammatory mediator, interleukin (IL) 6, leucocyte activation (polymorphonuclear leucocyte (PMN) CD11b receptor expression and plasma elastase-alpha1 proteinase inhibitor complex (E-alpha1PI)) and soluble endothelial adhesion molecule expression (soluble E-selectin (sE-selectin) and soluble intracellular adhesion molecule 1 (sICAM-1)) was performed in patients suffering blunt trauma without adult respiratory distress syndrome (ARDS) or multiple organ failure syndrome (MOFS). METHODS: Thirty-one patients with a mean Injury Severity Score (ISS) of 14 (range 9-57) were studied. Venous blood samples were collected within 6 h of injury and then at 1, 3, 5 and 7 days. Leucocyte CD11b expression was quantified by flow cytometry. Serum IL-6, plasma E-alpha1PI, sE-selectin and sICAM-1 were measured by enzyme-linked immunosorbent assay. RESULTS: Serum IL-6, CD11b expression and E-alpha1PI levels were significantly raised above control values (P < 0.0001) on admission, slowly returning towards control values over the study period (median IL-6, 140 pg/ml versus undetectable; CD11b, 14.8 versus 6.4 mean channel fluorescence units; E-alpha1 PI, 208 versus 52 microg/l). The sICAM-1 level rose to a median of 539 ng/ml at 5 days (control 243 ng/ml). The median sE-selectin level also progressively increased to a maximum level of 80 ng/ml at 5 days (control 49 ng/ml). Eleven patients developed postoperative sepsis. Significant differences in CD11b expression were seen at days 3, 5 and 7 and in E-alpha1 PI at 6 h, 24 h and 3 days in patients who subsequently developed sepsis (P < 0.05). Severe injury (ISS 16 or greater) was associated with significantly greater responses in these measurements. CONCLUSION: These data show that markers of inflammation are specifically stimulated by trauma even when ARDS and MOFS do not occur. The CD11b receptor on PMNs may be useful in screening patients destined to develop post-traumatic sepsis.

Adult↗
PubMed1998

Cytokine induction in hairless mouse and rat skin after topical application of the immune response modifiers imiquimod and S-28463.

ALDARA (imiquimod cream 5%) recently became available for the treatment of genital and perianal warts; however, the topical mechanism of action of imiquimod is not fully understood. Imiquimod, and its analogs R-842, S-27609, and S-28463, are potent anti-viral and anti-tumor agents in animal models. Much of the biologic activity of these compounds can be attributed to the induction of cytokines, including interferon-alpha, tumor necrosis factor-alpha, interleukins-1, -6, -8, and others. This study was performed to characterize the response of mice and rats to topical application of imiquimod and S-28463 and also to evaluate these agents in cultures of murine and human skin cells. Topical administration of imiquimod or S-28463 to the flanks of hairless mice and rats leads to increases in local concentrations of interferon and tumor necrosis factor in the skin. The concentrations of interferon and tumor necrosis factor were higher at the site of drug application than in skin from the contralateral flank or skin from untreated animals. Interferon-alpha mRNA levels were also elevated in the skin of mice after topical application of either imiquimod or S-28463. In vitro, both imiquimod and S-28463 induced increases in interferon and tumor necrosis factor in cultures of cells isolated from hairless mouse skin. Imiquimod also increased interleukin-8 concentrations in human keratinocyte and fibroblast cultures, whereas S-28463 induced increases in tumor necrosis factor in fibroblast cultures. These results demonstrate that imiquimod and S-28463 stimulate production of cytokines in the skin after topical application, which may play a major role in its activity in genital wart patients.

Adjuvants, Immunologic↗