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Biomedical subjects

L A Robinson

Publications and source records attributed to L A Robinson.

At least 37 records · Page 2Linked to original sources

Bone localization.

Accurate staging of malignancies is essential to guide the clinician in selecting the most appropriate therapy. Metastases to bone suggested by radionuclide bone scans must be proven histologically because of the high frequency of false-positive results. If the plain bone radiographs, however, are normal and there are no localizing symptoms, precise biopsy of the area of bone scan abnormality is usually difficult and time-consuming. The recently described intraoperative use of the hand-held gamma probe now allows for great accuracy and sensitivity in the radioisotope-guided open biopsy of clinically suspected bone metastases.

Biopsy↗

The role of adhesion molecules in human leukocyte attachment to porcine vascular endothelium: implications for xenotransplantation.

Many obstacles still prevent successful xenotransplantation of porcine donor organs. When hyperacute rejection is averted, transplanted pig organs are subject to acute vascular and cellular rejection. In autologous systems, leukocyte recruitment into inflamed tissues involves selectins, integrins, and Ig family members. To determine whether these mechanisms allow human leukocytes to effectively enter porcine grafts, the pathways by which human leukocytes adhere to TNF-alpha-stimulated porcine aortic endothelium were examined under static and physiologic flow conditions. L-selectin and E-selectin had overlapping functions in neutrophil capture and rolling, whereas Ab blockade of E-selectin and the beta2 integrins inhibited firm arrest of rolling neutrophils. Combined blockade of selectins and beta2 integrins resulted in negligible human neutrophil attachment to pig endothelium. Lymphocyte attachment to porcine endothelium was primarily L-selectin mediated, whereas beta2 integrin and VCAM-1/very late Ag-4 (VLA-4) interactions promoted static adhesion. Concurrent beta2 integrin, VLA-4, VCAM-1, and L-selectin blockade completely inhibited lymphocyte attachment. Thus, interactions between leukocyte-endothelial cell adhesion receptor pairs remained remarkably intact across the human-porcine species barrier. Moreover, disrupting the adhesion cascade may impair the ability of human leukocytes to infiltrate a transplanted porcine organ during rejection.

Animals↗

Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow.

Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular interactions between fractalkine (FKN), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, and its receptor (CX3CR1) in leukocyte capture, firm adhesion, and activation under physiologic flow conditions. Immobilized FKN fusion proteins captured resting peripheral blood mononuclear cells at physiologic wall shear stresses and induced firm adhesion of resting monocytes, resting and interleukin (IL)-2-activated CD8(+) T lymphocytes and IL-2-activated NK cells. FKN also induced cell shape change in firmly adherent monocytes and IL-2-activated lymphocytes. CX3CR1-transfected K562 cells, but not control K562 cells, firmly adhered to FKN-expressing ECV-304 cells (ECV-FKN) and tumor necrosis factor alpha-activated human umbilical vein endothelial cells. This firm adhesion was not inhibited by pertussis toxin, EDTA/EGTA, or antiintegrin antibodies, indicating that the firm adhesion was integrin independent. In summary, FKN mediated the rapid capture, integrin-independent firm adhesion, and activation of circulating leukocytes under flow. Thus, FKN and CX3CR1 mediate a novel pathway for leukocyte trafficking.

Cell Adhesion↗

Intraoperative gamma probe-directed biopsy of asymptomatic suspected bone metastases.

BACKGROUND: Radioisotope bone scanning is frequently used in staging malignancies. However, false-positive results are common, and biopsy is usually required. In the absence of plain radiographic abnormalities or local symptoms, localization of the area of abnormal tracer activity at the time of open rib or sternum biopsy may be difficult. It often requires resection of a large portion of one or more ribs or the sternum to assure that biopsy of the target area was performed. In this setting, a small gamma probe underwent evaluation as an aid to precise intraoperative localization of increased tracer activity in the target bone. METHODS: Ten patients with asymptomatic suspected osseous chest metastases by radioisotope bone scanning but with normal plain radiographs underwent open biopsy of 13 ribs and 1 sternum. Six to 12 hours before operation, each received an intravenous injection of 28 mCi of technetium-99m oxidronate. The hand-held, pencil-sized gamma probe in a sterile sleeve was used to localize the area of greatest activity in the target bone, once the bone was exposed through a small incision. Biopsy of a 3-cm length of rib or portion of sternum was performed. In the first two rib biopsies, an intraoperative radiograph with a radiopaque marker on the rib confirmed that the correct rib was selected for biopsy. Intraoperative radiographs were not done on later cases. RESULTS: The mean ratio of hot spot activity on the targeted rib to background counts on adjacent ribs was 1.65 +/- 0.22 (range, 1.35 to 2.05), and the difference was easily discernible intraoperatively. The ratio of hot spot activity on the sternum was somewhat lower (1.22), but the target area was still easy to detect. An abnormal diagnosis to account for the increased tracer activity was found in each of the 13 ribs and 1 sternal biopsy in all 10 patients: metastatic squamous cell carcinoma (1 rib), metastatic prostatic adenocarcinoma (1 rib), lymphoma (2 ribs), localized hypercellular marrow (1 rib), medullary fibrosis/Paget's disease of the bone (2 ribs), localized fibrosis/granulation tissue (1 rib), enchondroma (3 ribs), and chondroma (2 ribs, 1 sternum). The difference in background counts to hot spot activity was best with injection of the tracer 6 hours before operation. CONCLUSIONS: The intraoperative use of gamma counting is an easy, highly accurate aid (100% sensitivity) to localize areas of abnormal radioisotope uptake in suspected asymptomatic rib and sternal metastases. Use of this technique obviates the need to obtain intraoperative localizing radiographs to confirm accurate rib identification, thereby decreasing operative time.

Adenocarcinoma↗

Pleural tenting during upper lobectomy decreases chest tube time and total hospitalization days.

OBJECTIVE: A prolonged air leak after an upper lobectomy is a major determinant of morbidity and hospital stay. Creation of a pleural tent after upper lobectomy was used to investigate whether obliterating the usual postoperative intrapleural apical space with the parietal pleura would help shorten chest tube time. METHODS: From August, 1994, through January, 1997, 48 consecutive patients undergoing an isolated upper lobectomy for a neoplasm were reviewed. Twenty-eight patients had creation of a pleural tent and 20 patients did not. Demographic and clinical profiles of both groups were not significantly different. Chest tubes were removed when there was no air leak for 48 hours and chest tube drainage was less than 75 ml per 8 hours. RESULTS: The tented patients had significantly shorter mean air leak (tented 1.6 +/- 0.3 days vs nontented 3.9 +/- 1.2 days, p = 0.04), mean chest tube total drainage (tented 1619.5 +/- 95.5 ml vs nontented 2476.3 +/- 346.4 ml, p = 0.009), mean chest tube duration (tented 4.0 +/- 0.2 days vs nontented 6.6 +/- 1.0 days, p = 0.004), mean total hospitalization time (tented 6.4 +/- 0.4 days vs nontented 8.6 +/- 1.0 days, p = 0.02). No operative deaths occurred. Morbidity was not significantly different between groups. CONCLUSIONS: (1) Creation of a pleural tent at the time of upper lobectomy appears to significantly reduce chest tube time and shorten hospitalization. (2) No morbidity or mortality was associated with this simple, quick procedure. (3) Surgeons should consider creation of a pleural tent at the time of upper lobectomy.

Aged↗

The relationship between smoking and body weight in a population of young military personnel.

Evidence indicates that middle-aged smokers weigh less than nonsmokers and that smoking cessation reliably produces weight gain, but recent studies have questioned the weight control "benefits" of smoking in younger populations (the time that people typically initiate smoking). The relationship between smoking and body weight was evaluated in all U.S. Air Force Basic Military Training recruits during a 1-year period (n = 32,144). Those who smoked prior to Basic Military Training (n = 10,440) were compared to never smokers or experimental smokers. Results indicated that regular-current smoking had no relationship to body weight in women (p > .05) and a very small effect in men (p < .05). Ethnicity, education, income, and duration and intensity of smoking did not affect the relationship between smoking and body weight. It was concluded that smoking has no effects on the body weights of young women and minimal effects in young men.

Adolescent↗

Gender and ethnic differences in young adolescents' sources of cigarettes.

OBJECTIVE: To identify the sources used by young adolescents to obtain cigarettes. DESIGN: In early 1994 a survey assessing usual sources of cigarettes and characteristics of the respondents was administered in homeroom classes. SETTING: A large urban, predominantly African American school system. SUBJECTS: A population-based sample of 6967 seventh graders averaging 13 years of age. MAIN OUTCOME MEASURE: Reports of usual sources of cigarettes. RESULTS: At this age level, young smokers were more likely to get cigarettes from friends (31.2%) than buy them in stores (14.3%). However, the odds of purchasing varied for different groups of children. Regular smokers were much more likely (48.3%) to have purchased cigarettes than experimental smokers (9.6%), p < 0.001. Girls were less likely to have bought their cigarettes than boys (p < 0.001), and black smokers were less likely to have purchased cigarettes than white children (p < 0.001). Results suggested that family members who smoke may constitute a more important source of tobacco products than previously recognised, particularly for young girls. CONCLUSIONS: In this middle-school sample, peers provided the major point of cigarette distribution. However, even at this age, direct purchase was not uncommon. Sources of cigarettes varied significantly with gender, ethnicity, and smoking rate.

Adolescent↗

Appearance of immune complex glomerulonephritis following the onset of type I diabetes mellitus in a child.

Renal disease is a frequent late complication of type I diabetes mellitus, occurring almost entirely in adult patients. Typical diabetic nephropathy is characterized by proteinuria, and by the histological lesions of mesangial expansion and basement membrane thickening. We report an interesting case of a 3-year-old boy who developed immune complex glomerulonephritis with nephrotic syndrome 2 months after the onset of insulin-dependent diabetes mellitus.

Biopsy↗

Predictors of risk for different stages of adolescent smoking in a biracial sample.

This investigation was designed to identify the risk factors associated with different stages of cigarette use in a large biracial adolescent sample. A questionnaire assessing smoking habits and variables thought to be related to smoking was administered to 6,967 7th graders. Analysis revealed that the best predictor of experimentation with cigarettes was the perception that they were easily available. Regular smoking appeared to be heavily influenced by cost. Social influences contributed to both experimental and regular smoking, but the impact of social models varied with ethnicity and gender. Analysis further revealed that weight-related variables were closely tied to regular smoking. Implications of the findings for smoking prevention programs are discussed.

Adolescent↗

Ethnic and gender differences in risk factors for smoking onset.

The purpose of this investigation was to explore gender and ethnic differences in the prevalence of risk factors for smoking onset. As part of a larger study, 6,967 seventh graders completed a questionnaire measuring variables shown in previous research to predict cigarette smoking. The results indicated that at this age level, risk factors for smoking initiation are less prevalent among African Americans than European American youth and among girls relative to boys. These findings are consistent with the lower incidence of smoking among African Americans and girls at this young age. Future research should examine changes in risk factors over time to determine whether such changes accompany the rising smoking rate typically observed among girls and African Americans later in adolescence.

Adolescent↗

The ability of children with specific language impairment to access and participate in an ongoing interaction.

This study investigated the ability of 6 children with specific language impairment (SLI), ages 8;10 to 12;5 (years; months), to enter and participate in an ongoing dyadic interaction. Performance was compared to that of 6 chronological age-matched (CA) peers and 6 language-similar (LS) peers. All children in the LS and CA groups successfully accessed the interaction, and most did so quickly. Two children from the SLI group did not access, and the 4 remaining subjects required varying amounts of time to access. Following successful access, the triadic interactions of subjects were examined. The accessing children with SLI talked significantly less, were addressed significantly less, and collaborated less than either of the partners within their triads. Few significant differences were observed between LS or CA children and their partners.

Child↗

Chronic dieting and the belief that smoking controls body weight in a biracial, population-based adolescent sample.

OBJECTIVE: To evaluate the prevalence of weight concerns and smoking for body weight reasons as a function of race and gender. DESIGN: A questionnaire measuring a number of factors thought to be predictive of smoking was administered. SETTING: The Memphis (Tennessee) school system. PARTICIPANTS: Participants were 6961 seventh-grade students (mean age 13 years). This population consisted of 80.8% black children, 16.5% white children, and 2.7% of other ethnic origins. MAIN OUTCOME MEASURES: Weight concerns were assessed using items from a restraint scale. Students were questioned regarding their smoking status, beliefs that smoking controls body weight, and their own weight-control smoking behaviour. RESULTS: Dietary restraint interacted with race in that, whereas white girls scored the highest on dietary restraint, black boys scored higher on dietary restraint than white boys. Almost 40% of subjects at this school level believed that smoking controls their body weight. Of the regular smokers, 12% indicated they have smoked to control their weight, with white girls endorsing this belief significantly more than other respondents. CONCLUSIONS: The propensity to smoke for weight control reasons, previously described by other researchers among white females of college and high-school age, was also found among this sample of students of junior high school age.

Adolescent↗

Teaching the teachers--a needs assessment of tutors for a new clinical skills course.

There is an increasing trend in undergraduate education towards teaching clinical skills from a community base. A new clinical curriculum was introduced in Newcastle upon Tyne in 1995, beginning with an integrated clinical skills course. Although the attitudes and views of general practitioners (GPs) towards community-based clinical teaching have previously been reported, their perceived training needs have not been formally identified. The aims of this study were to identify the competencies needed by GPs for community-based clinical skills teaching, to compare and contrast these needs with their hospital colleagues, and to use the results to develop a teaching programme for the clinical tutors involved in the new course. In order of priority, the GPs and hospital tutors expressed similar needs: small-group teaching skills, assessing student needs, giving effective feedback and assessment of student performance, with a preference for the teaching to be organized within local teaching units. Most GPs and hospital tutors (73 and 69%, respectively) requested a distance-learning pack to complement the teaching. General practitioners rated resources for improving their individual clinical skills more highly than their hospital colleagues: for example, videotapes demonstrating examination techniques. Forty-six per cent of GP tutors had received some formal training in teaching methods compared to 29% of hospital tutors. The implications of the results for developing a 'Teaching the Teachers' course for clinical tutors are discussed.

Clinical Competence↗

Use facilitated case discussions for significant event auditing.

An important type of review undertaken routinely in health care teams is analysis of individual cases. This informal process can be turned into a structured and effective form of audit by using an adaptation of the "critical incident" technique in facilitated case discussions. Participants are asked to recall personal situations that they feel represent either effective or ineffective practice. From such review of individual cases arise general standards to improve the quality of care. On the basis of a study of audit of deaths in general practice, we describe how to implement such a system, including forming and maintaining the discussion group, methodology, and guidelines for facilitators. Problems that may arise during the case discussions are outlined and their management discussed, including problems within the team and with the process of the discussions.

Communication↗

Escherichia coli verotoxin binding to human paediatric glomerular mesangial cells.

Haemolytic uraemic syndrome (HUS) remains the leading cause of acute renal failure in children. Although an Escherichia coli-produced verotoxin (VT) has been implicated in the pathogenesis of HUS, the precise mechanisms of disease are not well defined. We hypothesise that the pathogenesis of renal failure in HUS includes the binding of E. coli VT to the glomerular mesangial cell, with consequent effects on renal function. Using human paediatric mesangial cells, we studied the binding and biological effects of the purified verotoxin VT-1. We isolated, purified and characterised paediatric glomerular mesangial cells. The mesangial cells were characterised by their immunoreactivity with both smooth muscle actin and vimentin antibodies, and lack of immunoreactivity with cytokeratin or factor VIII antibodies. Using an fluorescein isothiocyanate-conjugated VT (10(-7)-10(-8) M), we demonstrated specific binding to the mesangial cell membrane by immunofluorescence microscopy. We also demonstrated a dose-dependent inhibition of mesangial cell mitogenesis at concentrations from 10(-9) to 10(-17) M. Our data demonstrate that VT-1 binds to paediatric human glomerular mesangial cells and this binding results in specific biological actions, including an inhibition of cell mitogenesis.

Bacterial Toxins↗

Myocardial protection for acquired heart disease surgery: results of a national survey.

To study current myocardial protection practices, all 4,393 United States board-certified thoracic surgeons were surveyed in 1992. Of the 1,413 respondents (32% total response), 936 are in active practice dealing with acquired heart disease. Based on their frequency of cases, respondents perform approximately 32% of all acquired heart disease operations in the United States yearly and individually average 157 patients/year. For myocardial protection, 98% of respondents routinely use cardioplegic arrest. The primary method of cardioplegia delivery is antegrade 36%, retrograde 4%, and a combination of antegrade and retrograde 60%. The types of cardioplegic solutions used are blood 72%, crystalloid 22%, and oxygenated crystalloid 6%. Continuous warm blood cardioplegia is used by 10% of respondents, whereas most (75%) have adopted a skeptical "wait and see" attitude or have abandoned it (6%). Overall, most surgeons (78%) report that they are very satisfied with their present methods of myocardial protection, whereas only 2% are dissatisfied. Still, the three areas believed most important for future research are reperfusion injury (74%), acutely infarcting myocardium (61%), and metabolic enhancers in cardioplegia (58%).

Adult↗

c-myc antisense oligodeoxyribonucleotides inhibit proliferation of non-small cell lung cancer.

BACKGROUND: Mutation or deregulation of certain cellular genes (protooncogenes) results in expression of proteins that appear to promote malignant transformation. Human non-small cell lung cancer has been documented to express many such oncogenes including c-myc, bcl-2, and mutant p53. Antisense oligodeoxyribonucleotides (ASODN) complementary to these oncogenes were tested on three non-small cell lung cancer cell lines for their efficacy in inhibiting cellular proliferation and oncoprotein expression. METHODS: Established non-small cell lung cancer cell lines A427, SKMES-1, and A549 were grown in the presence of ASODNs complementary to messenger RNA of c-myc, bcl-2, p53, or controls at 1 mumol/L or 10 mumol/L concentrations for 4 or 10 days. Cellular proliferation was measured by tritiated thymidine uptake. Flow cytometry was used to quantitate oncoprotein expression. Intranuclear ASODN uptake was documented by fluoresceine-tagged ASODNs. RESULTS: Fluoresceine-tagged ASODNs were readily taken up by all cell lines. c-myc, as well as bcl-2 and p53 ASODNs, were found to inhibit proliferation of all cell lines significantly compared with controls, most notably in line A549 (40.1% +/- 7.1% of control, p = 0.000 with c-myc ASODN). Antisense c-myc reduced c-myc protein by as much as 71.3% in A427, although protein levels were only minimally reduced in the viable cells of the other lines. CONCLUSIONS: c-myc ASODNs inhibit proliferation of non-small cell lung cancer cell lines as well as reduce c-myc protein expression. Antisense bcl-2 and p53 also cause similar growth inhibition. These results suggest a critical role for activation of these oncogenes in the growth of cultured lung cancer cells. Furthermore, the efficacy and rapid cellular uptake of ASODNs support the potential role of antisense targeting of oncogene expression for pharmacologic control of non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗