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Biomedical subjects

S Sloan

Publications and source records attributed to S Sloan.

At least 37 records · Page 2Linked to original sources

Improved survival following massive transfusion in patients who have undergone trauma.

HYPOTHESIS: Survival following massive transfusion in patients who have undergone trauma has improved during the past 10 years. DESIGN: Retrospective cohort study. SETTING: Academic level I trauma center in an urban community. PATIENTS: All patients who underwent trauma and who received greater than 50 U of packed red blood cells or whole blood in the 48 hours following admission to the emergency department. INTERVENTIONS: Data were obtained from blood bank records, the trauma registry, patient medical records, and hospital purchasing records. Patients were divided into 2 groups for comparison (early [1988-1992] and late [1993-1997] periods). MAIN OUTCOME MEASURES: Survival and changes in trauma care provision. RESULTS: Survival following massive transfusion in patients who have undergone trauma has significantly increased during the past 10 years (16% vs 45%, early vs late period, P = .03). Factors associated with poor outcome included male sex, major vascular injury, high Injury Severity Score, severe acidosis, prolonged hypotension, refractory hypothermia, and decreased use of platelet transfusion (all P<.05). In the later period, there was more aggressive correction of coagulopathy, more efficient use of warming measures, decreased operative times for the initial operation, and increased use of component therapy (all P<.05). CONCLUSIONS: Survival following massive transfusion has significantly (P = .03) increased during the past 10 years. Factors that may have contributed to this include more effective and efficient rewarming procedures, improved application of damage control techniques, more aggressive correction of coagulopathy, and improved blood banking procedures.

Adult↗

Fine needle aspiration cytology (FNAC) of mammary granular cell tumour: a report of three cases.

This report describes the FNAC findings in three cases of granular cell tumour of the breast. The patients comprised two females aged 59 and 62 years and one male aged 28 years. All patients presented with a breast lump which was clinically and radiologically suspicious of malignancy. FNAs yielded moderately cellular specimens which on cytologic examipation consisted of groups of cells and single cells with small regular nuclei and abundant granular cytoplasm. Bare nuclei were also present but these did not have the characteristic bipolar appearance of myoepithelial cells. In two cases there was a granularity to the background. The aspirates were reported as equivocal or atypical, probably benign, and surgical biopsy was performed. Histological examination showed typical benign granular cell tumours with strong positive staining for S-100 protein. Pathologists should be aware that granular cell tumour may occur in or around the breast and should consider this diagnosis in aspirates containing a population of cells with regular nuclei and abundant granular cytoplasm. The main cytologic differential diagnoses are likely to be apocrine cells and histiocytes. The suspicion of a granular cell tumour should be heightened when these features are present in an aspirate from a clinically and radiologically suspicious mass. These cases highlight the role of the triple approach encompassing clinical, radiological and cytological features in the assessment of a breast lesion.

Adult↗

ATP does not affect fibrinogen binding to platelet GPIIbIIIa in systems free of signal transduction.

Recent studies have suggested that the platelet fibrinogen (Fg) receptor, platelet membrane glycoprotein IIbIIIa (GPIIbIIIa, or integrin alpha(IIb)beta(3)) is also an adenosine triphosphate (ATP) binding site, and that the binding of ATP can directly inhibit the Fg-binding function of GPIIbIIIa. However, any direct effect of ATP on GPIIbIIIa function in intact fresh platelets is difficult to distinguish from indirect inhibitory effects via competition with ADP or elevation of platelet cyclic AMP levels. We therefore studied effects of ATP on Fg binding to activated GPIIbIIIa on the following model particles: externally activated and fixed platelets, as well as latex particles and liposomes containing functionally competent activated GPIIbIIIa receptors for Fg. These particles have 'normal', activated GPIIbIIIa in terms of: (1) binding affinity, (2) specificity to Fg, and (3) conformational change(s) after Fg binding. These particles neither require nor respond to further activation in order to bind Fg. With these model particles, we showed that ATP does not have any direct effect on the binding of Fg to platelet GPIIbIIIa and platelet aggregation. These simplified model particles are useful tools in the mechanistic study of platelet GPIIbIIIa function and the interaction between platelet GPIIbIIIa and its ligands.

Journal Article↗

Recognition of core binding sites by bacteriophage integrases.

Bacteriophage integrases promote recombination between DNA molecules that carry attachment sites. They are members of a large and widely distributed family of site-specific recombinases with diverse biological roles. The integrases of phages lambda and HK022 are closely related members of this family, but neither protein efficiently recombines the attachment sites of the other phage. The nucleotides responsible for this specificity difference are located close to the points of recombinational strand exchange, within an integrase binding motif called the extended core binding site. There are four imperfectly repeated copies of this motif in each set of phage attachment sites, but only two, B' and C, contain major specificity determinants. When these specificity determinants were replaced by the corresponding nucleotides from a site with the alternative specificity, the resulting mutant was recombined by both integrases. Thus, the determinants act by impeding recombination promoted by the non-cognate integrase. We found that identical nucleotide substitutions within different core site copies had different effects on recombination, suggesting that integrase does not recognize each of the extended core binding sites in the same way. Finally, substitution at several positions in lambda integrase with the corresponding HK022-specific amino acids prevents recombination of lambda attachment sites, and this defect can be suppressed in an allele-specific manner by appropriate substitutions of HK022-specific nucleotides in the extended core binding sites.

Amino Acid Sequence↗

Resistance to murine hepatitis virus strain 3 is dependent on production of nitric oxide.

The strain-specific spectrum of liver disease following murine hepatitis virus type 3 (MHV-3) infection is dependent on inflammatory mediators released by macrophages. Production of nitric oxide (NO) by macrophages has been implicated in resistance to a number of viruses, including ectromelia virus, vaccinia virus, and herpes simplex virus type 1. This study was undertaken to define the role of NO in MHV-3 infection. Gamma interferon-induced production of NO inhibited growth of MHV-3 in a murine macrophage cell line (RAW 264.7). Viral inhibitory activity was reproduced by the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP), whereas N-acetyl-DL-pencillamine (NAP), an inactive analog of SNAP, had no effect. Electron microscopy studies confirmed the inhibitory effects of NO on viral replication. Peritoneal macrophages isolated from A/J mice known to be resistant to MHV-3 produced a fivefold-higher level of NO and higher levels of mRNA transcripts of inducible NO synthase in response to gamma interferon than macrophages from susceptible BALB/cJ mice. SNAP inhibited growth of MHV-3 in macrophages from both strains of mice to similar degrees. In vivo inhibition of NO by N-monomethyl-L-arginine resulted in loss of resistance to MHV-3 in A/J mice. These results collectively demonstrate a defect in the production of NO in macrophages from susceptible BALB/cJ mice and define the importance of endogenous NO in resistance to MHV-3 infection in resistant A/J mice.

Animals↗

Immunofiltration purification for urinary leukotriene E4 quantitation.

Leukotriene E4 (LTE4) is a major leukotriene metabolite in urine. Urinary LTE4 concentration is often utilized as an index of total leukotriene synthesis. A novel method employing immunofiltration for the purification of urinary LTE4 was developed. This immunofiltration method is based upon the addition of excess anti-LTE4 antibody to urine which binds LTE4. Separation of bound LTE4 (high M(r)) from high levels of unbound contaminants (low M(r)) is then accomplished by filtration through a 10,000 M(r) cut-off filter. The LTE4-antibody complex is separated by precipitation of the antibody with methanol which is subsequently removed by centrifugation. Following evaporation of the methanol, enzyme immunoassay is utilized for quantitation. This methodology was validated by determining the recovery of tritiated and unlabeled LTE4 added to urine and buffer and by comparison of results obtained with urine samples measured after HPLC purification (correlation r2 = 0.72). Reproducibility of the assay was assessed by analyzing the same sample on two different days (standard deviation of 18%). The mean urinary LTE4 levels in healthy subjects and asthmatics measured utilizing this method were found to be identical to levels determined by HPLC/immunoassay. The ease and accuracy of this assay make it amenable for the analysis of large numbers of samples.

Antibodies, Monoclonal↗

Interaction of RGD liposomes with platelets.

The interactions of platelets and liposomes with the tripeptide arginine-glycine-aspartic acid (RGD) as a surface ligand (RGD liposomes) were studied. The results suggest that the presence of the RGD ligand on the liposomes results in receptor-mediated mixing of lipid and aqueous contents of the liposomes and platelets. Mixing of the lipid and aqueous contents of RGD liposomes with platelets is approximately 4-9 times and 3-4 times greater than that for unlabeled liposomes, respectively. Measurements of the cytoplasmic free Ca2+ concentration in platelets, [Ca2+]i, show that the RGD liposomes have little effect on [Ca2+]i.

Animals↗

Orthotopic laryngeal transplantation: is it time?

The notion of returning phonatory and respiratory function by transplanting larynges has fascinated and challenged the minds of laryngologists for many years. In the past, the problems of revascularization, tissue rejection, and physiologic vocal fold motion have stymied the success of research in this area. Today, advances in microvascular surgery, graft versus host response, and selective reinnervation have made laryngeal transplantation a theoretical, if not a practical reality. Despite this progress, serious ethical and fiscal considerations remain unresolved. This report will discuss these advances as well as concerns and will present the current UCLA laryngeal physiology laboratory experience with canine laryngeal transplantation.

Animals↗

Determinants of gastroesophageal junction incompetence: hiatal hernia, lower esophageal sphincter, or both?

OBJECTIVE: To examine the effects of hiatal hernia and lower esophageal sphincter (LES) pressure on the competence of the gastroesophageal junction under conditions of abrupt increases in intra-abdominal pressure. DESIGN: Acute experiments. SETTING: University-hospital-based gastroenterology practice. PARTICIPANTS: Sixteen asymptomatic volunteers and 34 patients with endoscopic findings suggestive of hiatal hernia. INTERVENTION: A series of eight provocative maneuvers entailing abrupt changes in intra-abdominal pressure. MEASUREMENTS: Five radiographic measurements relevant to the presence and extent of hiatal hernia were made from videotaped barium-swallow examinations. Lower esophageal sphincter pressure was measured immediately before each maneuver. The percentage of maneuvers that resulted in gastroesophageal reflux was calculated as the reflux score. A stepwise regression analysis was then used to model the relation between measured variables of the gastroesophageal junction (manometric and radiographic) with reflux score. RESULTS: Patients with hiatal hernia had substantially higher reflux scores and lower LES pressures than either patients without hernias or volunteers. In diminishing order of significance, the terms in the model of susceptibility to reflux were axial length of hernia measured between swallows; LES pressure; and an interaction term in which a progressive increase occurred in the risk for reflux associated with a hypotensive lower esophageal sphincter as hernia size increased. CONCLUSIONS: Gastroesophageal junction competence during abrupt increases in intra-abdominal pressure is compromised by both hiatal hernia and low LES pressure. These factors interact with each other to determine susceptibility to reflux.

Abdomen↗

Induction of HLA class II molecules on human T cells: relationship to immunoregulation and the pathogenesis of AIDS.

Human T cells express HLA class II molecules upon activation. The factors that regulate the induction of expression of these molecules are for the most part unknown. Here we report preliminary results indicating that tumor necrosis factor-alpha (TNF-alpha) regulates the induction of cell-surface HLA-DR, DO, and DP molecules in human T cells stimulated with PHA. In contrast, recombinant interferon-gamma (rIFN-gamma), recombinant interleukin-1 alpha (rIL-1 alpha), or rIL-4 appear to have no effect on class II expression. The role of class II molecules on activated T cells is discussed in relationship to immunoregulation and the progression of HIV infection. Three non-mutually exclusive hypotheses are discussed. In the first hypothesis, we consider the role of these class II molecules in antigen presentation of endogenously synthesized HIV envelope by CD4+ cells. The second is a clonal inactivation of virus-specific helper T cells that might occur as a consequence of a direct T cell to T cell interaction and a bypass of the "accessory signal" normally delivered by antigen-presenting cells such as macrophages. The third is a molecular mimicry between HIV envelope proteins and HLA class II molecules, which may lead to the development of autoimmunity against CD4+ T-cell-expressing class II molecules.

Acquired Immunodeficiency Syndrome↗

Impairment of esophageal emptying with hiatal hernia.

Concurrent videofluoroscopy and manometry were used to analyze esophageal emptying during barium swallows in 22 patients with axial hiatal hernias and in 14 volunteers. Subjects were divided into three groups: (a) volunteers with maximal phrenic ampullary length less than 2 cm (controls); (b) patients or volunteers with maximal ampullary/hiatal hernia length greater than or equal to 2 cm that reduced between swallows (reducing-hernia group); and (c) patients with hernias that did not reduce between swallows. Complete esophageal emptying without retrograde flow was achieved in 86% of test swallows in the controls, 66% in the reducing-hernia group, and 32% in the nonreducing-hernia group (P less than 0.05). Impaired emptying in the reducing-hernia group was attributable to "late retrograde flow," whereby barium squirted retrograde from the hernia during emptying. Impaired emptying in the nonreducing-hernia group was attributable to "early retrograde flow" that occurred immediately after LES relaxation. The nonreducing-hernia group also had longer acid clearance times than the controls (P less than 0.05). We conclude that gastroesophageal junction competence is severely impaired in patients with nonreducing hiatal hernias, suggesting a mechanism whereby this subgroup of hiatal hernia is involved in the pathogenesis of reflux disease.

Adolescent↗

Physical fitness effects on substance abuse risk factors and use patterns.

In this study, seventy-four adolescents in either a school, community or hospital based drug intervention program received and eight to nine week structured fitness activity class as an integrated element of their respective prevention or treatment program. Prepost assessments indicated significant gains in the field fitness tests of one mile run, 1 minute situp, 1 minute pushup, percent fat and flexibility for the total sample. Based upon prepost change on the one mile run time (less than 1:00) subjects were categorized as improvers (n = 38) and non-improvers (n = 36). Improvers demonstrated a significant increase in the self concept risk factor (Piers Harris Self Concept Scale) and a significant decrease in anxiety and depression risk factors (General Well-Being Scale) compared to the non-improvers. At posttest, the improvers self reported substance use patterns were significantly lower compared to the non-improvers for percentage of the sample who were multiple drug users and alcohol uses per week and were significantly higher for the percentage of the sample demonstrating total abstinence. These findings are suggestive of the usefulness of physical training as a supplemental intervention for adolescent substance abusers.

Adolescent↗

Excellence in nursing management. Competency-based selection and development.

The promotion of nurses to nurse management positions usually is based on traditional criteria, such as formal education, professional experience, and technical expertise. An exploratory Hay Group pilot study, however, shows that these criteria have little correlation to a candidate's probability of success as a manager. Instead, an entirely different set of desirable nurse manager competencies was revealed. According to the pilot study, qualities such as self-confidence, high achievement orientation, analytical thinking, and persuasive skills are far more important determinants of success among nurse managers.

Competency-Based Education↗

Enucleation and psychic trauma.

The surgeon must be aware of the psychological impact on a patient when performing an enucleation. The surgeon should offer patients psychiatric assistance to deal with the trauma of an enucleation. The formation of a group therapeutic organization may be a viable approach to gathering patients to talk about their concerns. "Enucleations Anonymous" is proposed.

Depression↗

Flow cytometric analysis of human uterine sarcomas and cell lines.

Flow cytometric techniques were used to characterize multiple human uterine sarcomas and cell lines derived from some of these tumors. Analysis of DNA content showed that 9 of the 11 uterine sarcomas investigated were composed of at least one aneuploid population as well as a distinct diploid population. These data indicate that aneuploidy, as measured by flow cytometry, is a characteristic more common to uterine sarcomas than that previously reported for uterine adenocarcinomas. Unlike the original tumors, the cell lines established from three of the sarcomas contained predominantly diploid populations with only minor aneuploid populations. Treatment of one of the sarcoma cultures with tumor promoters did not result in an increase in the aneuploid populations. Tumors which arose in nude mice upon transplantation of two of the sarcomas did not contain the same distribution of tumor subpopulations as found in the original sarcomas. Apparently, the in vitro culture and and in vivo nude mouse conditions were not appropriate for maintaining the original equilibrium between the aneuploid and diploid subpopulations but instead provided a selective environment that resulted in the preferential growth of only certain tumor populations. Dual-parameter analysis of DNA content and alkaline phosphatase levels of one of the sarcomas were useful for distinguishing the aneuploid from the diploid population coexisting in this tumor. Our data suggest that flow cytometry is a valuable tool to analyze the characteristics of the tumor populations residing in primary uterine sarcomas as well as to determine which of these tumor subpopulations survive in culture and transplantation to nude mice.

Alkaline Phosphatase↗

Linking human resources and cost containment strategies.

Because hospitals are labor intensive, strategies for managing and controlling personnel costs are critical. The author examines the necessary linkages between a hospital's business and human resource strategies, how management style may affect the success of those strategies, and appropriate compensation awards for employees.

Cost Control↗