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Biomedical subjects

D Lyon

Publications and source records attributed to D Lyon.

At least 19 recordsLinked to original sources

Cefepime vs. Ampicillin/Sulbactam and Aztreonam as antibiotic prophylaxis in neurosurgical patients with external ventricular drain: result of a prospective randomized controlled clinical trial.

INTRODUCTION: We aimed to find out whether single board spectrum antibiotic prophylaxis was as good as dual specific antibiotic prophylaxis in neurosurgical patients with external ventricular drain (EVD) in situ. METHOD: In a 2-year period, 255 eligible patients were recruited. Patients were randomized into two groups of antibiotic prophylaxis as long as the ventricular catheter in situ. Group A employed Cefepime 2G 12 hourly and Group B employed dual antibiotics as Ampicillin/Sulbactam 3 g 8 hourly and Aztrenam 2 g 8 hourly. RESULTS: There was no statistically significant difference in cerebrospinal fluid (CSF) infection rate with 14 patients (11.5%) in group A (Cefepime prophylaxis) and eight patients (6.0%) in group B (dual prophylaxis with Ampicillin/Sulbactam and Aztrenam) had CSF infection (P=0.18). There was also no statistical significant difference between wound infection rate happened in eight patients (6.6%) in Group A and three patients (2.3%) in Group B (P=0.17). There was no statistical significant difference in extracranial infection rate between both groups (P=0.70). CONCLUSION: Single board spectrum antibiotic prophylaxis with Cefepime was an effective alternative regimen for neurosurgical patients with an EVD in situ.

Adolescent↗

Incidence and risk factors for microbial keratitis in Hong Kong: comparison with Europe and North America.

PURPOSE: To establish the incidence, etiology and risk factors for microbial keratitis (MK) in Hong Kong. METHODS: Two hundred and twenty-three new cases of presumed MK were recruited over a period of 17 months and comprehensive microbiologic studies performed. A nested case-control study was pursued for patients wearing contact lenses (CLW) to determine risk factors for MK with regards to types of CLW and hygiene practice. RESULTS: Of the 223 patients recruited, 59 (26%) wore contact lenses. Corneal scrapes yielded positive cultures from 77 patients (35% overall, 56 non-CLW, 21 CLW). Two hundred and six CLW volunteers were recruited to participate in the case-control study, of whom 135 were matched with 45 CLW patients. The annual incidence of MK was 0.63 per 10,000 population and 3.4 per 10,000 CLW with rates for daily, extended and rigid lens wear of 3.09, 9.30 and 0.44 per 10,000 CLW respectively. Pseudomonas aeruginosa was the dominant bacterial pathogen. Six cases of Acanthamoeba keratitis occurred, five in CLW (incidence 0.33 per 10,000 CLW) and one following corneal abrasion. Non-CLW developed MK at a peak age of 73, which is 10 years younger than expected for Scotland and USA. CONCLUSIONS: Previous ocular surface disease and trauma were the main risk factors for MK in Hong Kong. CLW appears at least as safe as that found in Scotland and the USA. Acanthamoeba keratitis was detected but with an incidence rate five times lower than Scotland. Factors predisposing hydrogel CLWs to MK, that were statistically significant, included overnight wear, poor hygiene and smoking.

Acanthamoeba Keratitis↗

Failure of regular external ventricular drain exchange to reduce cerebrospinal fluid infection: result of a randomised controlled trial.

BACKGROUND: It is controversial whether regular changes of external ventricular drains can reduce cerebrospinal fluid (CSF) infection. OBJECTIVE: To carry out a randomised controlled clinical trial over a two year period to determine whether a regular change of ventricular catheter every five days could reduce CSF infection and improve outcome. METHODS: 103 patients requiring external ventricular drains for more than five days and with no evidence of concurrent CSF infection were studied. The patients were randomised to regular change of ventricular catheter (every five days) and no change unless clinically indicated. RESULTS: The CSF infection rates were 7.8% for the catheter change group and 3.8% for the no change group, respectively (rate ratio = 1.80, 95% confidence interval 0.33 to 9.81, p = 0.50). No significant difference was found in intensive care unit stay, ward stay, or clinical outcome between the two groups. CONCLUSIONS: Regular changes of ventricular catheter at five day intervals did not reduce the risk of CSF infection. A single external ventricular drain can be employed for as long as clinically indicated.

Acinetobacter Infections↗

The opposing roles of the Akt and c-Myc signalling pathways in survival from CD95-mediated apoptosis.

Expression of the proto-oncogene c-myc stimulates cell proliferation in the presence of the appropriate survival factors and triggers apoptosis in their absence; this dual capacity ensures that cell growth is restricted to the correct paracrine environment and is thereby strictly controlled. Recently our laboratory demonstrated that c-Myc-induced apoptosis requires the CD95 death receptor pathway and that insulin-like growth factor (IGF-1) signalling suppresses this killing. To investigate further the links between c-Myc and IGF-1 pathways in CD95-induced apoptosis, we examined the effects of c-Myc and a downstream IGF-1 survival kinase, Akt, on killing mediated by CD95 and its recruited effector proteins (FADD and caspase-8). Here, we show that c-Myc activation does not exacerbate killing induced by FADD or pro-caspase-8, which narrows the point at which c-Myc exerts its action downstream of the interaction of CD95 with its ligand and upstream of FADD. We show further that activated Akt suppresses CD95-induced apoptosis and that Akt exerts its activity at a point downstream of FADD but upstream of caspase-8. These results restrict the possible mechanisms by which CD95-induced apoptosis is modulated by death signals and survival factors.

3T3 Cells↗

Specific TrkA survival signals interfere with different apoptotic pathways.

Survival signalling by ligand-activated tyrosine kinase receptors plays a crucial role in maintaining the balance between cell viability and apoptosis in multicellular organisms. To identify receptor domains and pathways involved in survival signalling, the nerve growth factor receptor TrkA was expressed in Rat-1/MycER fibroblasts. We demonstrate that wt-TrkA receptor delays c-Myc-, U.V.- and Cycloheximide-induced apoptosis and activates targets such as the mitogen-activated protein kinase (MAPK) Erk2 and the serine/threonine kinase Akt/PKB, both of which have been implicated in survival signalling. TrkA mutated within its SHC binding site (Y490F) delays c-Myc-induced apoptosis without activating endogenous Akt/PKB. In contrast, the TrkA Y490F mutant receptor does not delay U.V.-induced apoptosis whilst TrkA mutated at its PLC-gamma binding site (Y785F) is capable of protecting from apoptosis induced by c-Myc or U.V. treatment. The double mutant TrkA YY490/785FF fails to block either of these two apoptotic stimuli. While P13-kinase inhibitors LY294002 and Wortmannin completely block survival signalling following U.V. treatment, neither drug affects the ability of TrkA to block c-Myc-induced apoptosis. We show that the Akt/PKB pathway is essential for NGF stimulated TrkA survival signalling in the case of U.V.-induced apoptosis, but that apoptosis induced by c-Myc is also blocked by a novel, Akt/PKB-independent, pathway. These observations suggest that TrkA can activate different survival signalling pathways, which can interfere with specific apoptotic pathways.

Animals↗

Requirement for the CD95 receptor-ligand pathway in c-Myc-induced apoptosis.

Induction of apoptosis by oncogenes like c-myc may be important in restraining the emergence of neoplasia. However, the mechanism by which c-myc induces apoptosis is unknown. CD95 (also termed Fas or APO-1) is a cell surface transmembrane receptor of the tumor necrosis factor receptor family that activates an intrinsic apoptotic suicide program in cells upon binding either its ligand CD95L or antibody. c-myc-induced apoptosis was shown to require interaction on the cell surface between CD95 and its ligand. c-Myc acts downstream of the CD95 receptor by sensitizing cells to the CD95 death signal. Moreover, IGF-I signaling and Bcl-2 suppress c-myc-induced apoptosis by also acting downstream of CD95. These findings link two apoptotic pathways previously thought to be independent and establish the dependency of Myc on CD95 signaling for its killing activity.

3T3 Cells↗

Attention and nontarget effects in the location-cuing paradigm.

Three experiments were conducted in order to determine whether irrelevant items presented outside the focus of attention would affect the identification of a precued target. A peripheral cue indicated one of eight possible locations in a circular array, centered on fixation with a radius of 5.25 degrees. After a variable interval (0-200 msec), eight characters were presented briefly and masked. In each experiment, there was an effect of the identity of the characters at the seven noncued locations (the nontargets) on the accuracy of identification of the target. When there were more nontargets identical to the target, accuracy was higher than when there were fewer nontargets identical to the target. Nontargets consistently affected performance despite incentives to focus only on the target.

Adult↗

In-vitro activity of quinolones and macrolides against mycobacteria.

The activities of eight quinolones (ciprofloxacin, clinafloxacin, levofloxacin, ofloxacin, A-80556, sparfloxacin, temafloxacin and tosufloxacin) and three macrolides (azithromycin, clarithromycin and erythromycin) against 98 clinical isolates of Mycobacterium tuberculosis and 120 isolates of five different atypical mycobacterial species including 20 Mycobacterium kansasii, 25 Mycobacterium scrofulaceum, 25 Mycobacterium avium/intracellulare, 25 Mycobacterium chelonae and 25 Mycobacterium fortuitum were determined with the Middlebrook 7H9 broth macrodilution method. Sparfloxacin, clinafloxacin, levofloxacin, ciprofloxacin and ofloxacin were active against M. tuberculosis (MIC90 0.06-0.5 mg/L; MBC90 0.125-2.0 mg/L). However, higher MIC90S and MBC90S of these quinolones were obtained for strains of multi-drug resistant M. tuberculosis. The macrolides tested had poor activity against M. tuberculosis isolates (MIC90 > 8.0 mg/L). Furthermore, high MIC90S of the quinolones and macrolides (2.0 to 8.0 mg/L) were obtained for clinical isolates of atypical mycobacteria, with the exception of clarithromycin against M. kansasii (MIC90 = 1.0 mg/L) and sparfloxacin against M. scrofulaceum (MIC90 = 1.0 mg/L).

4-Quinolones↗

Comparison of flow cytometric DNA content analysis of fresh and formalin-fixed paraffin-embedded solid neoplasms.

In an attempt to compare results of fresh and fixed tissue flow cytometric DNA analysis we analyzed paraffin blocks of 87 solid tumors; 67 of these were DNA aneuploid and 20 were DNA euploid by fresh flow cytometric analysis. Forty-two aneuploid tumors and all diploid tumors were concordant (71.3% concordance), whereas 25 of 67 (37%) aneuploid tumors appeared diploid on fixed tissue analysis. Reasons for discordance included loss of small aneuploid peaks, merging of G1/G0 peaks of diploid and aneuploid stemlines giving a broad G1/G0 peak, and masking of near-tetraploid aneuploid peaks by the G2/M peak in fixed tissue. S-phase fraction could be determined in 51 of 67 (76%) aneuploid cases analyzed fresh and 29 of 42 (69%) concordant aneuploid cases analyzed from fixed tissues. All parameters were consistently higher in the fixed tissue: S-phase fraction (mean = 18.29% versus 12.82%), coefficient of variation of diploid G1/G0 peak (5.62% versus 2.11%), and DNA index (1.79 versus 1.69). We conclude that significant differences exist between flow cytometric data obtained from analysis of fresh versus fixed tissues and therefore prognostic correlations made on the basis of results of fixed tissue flow cytometric analysis may not necessarily parallel those of fresh tissue studies.

Aneuploidy↗

Evaluation of three culture media and their combinations for the isolation of Mycobacterium tuberculosis from pleural aspirates of patients with tuberculous pleurisy.

The abilities of three culture systems to detect Mycobacterium tuberculosis from 480 pleural aspirate specimens in 347 patients were compared. The systems were the Bactec 12B radiometric detection system (Bactec 12B), the Middlebrook 7H9 broth (7H9), and two solid media including one pyruvate enriched Lowenstein-Jensen slope (LJP) and one non-selective Middlebrook 7H11 agar slope (7H11). In the 116 specimens obtained from 85 patients of confirmed pleural tuberculosis for the isolation of Mycobacterium tuberculosis, the diagnostic yields were 33 (39%) cases from Bactec 12B, 24 (28%) cases from 7H9 and 21 (25%) cases from LJP/7H11, with median detection times of 18, 47.5 and 44 days respectively. Thirteen isolates were recovered by the Bactec 12B only, 9 by the 7H9 broth only, and 2 by the LJP/7H11 agar only. The use of a combination of the three culture systems substantially increased the diagnostic yield to 47% over the individual systems. These results show that a significantly greater and faster diagnostic yield can be obtained by including Bactec 12B in pleural aspirate cultures for the recovery of Mycobacterium tuberculosis.

Biopsy, Needle↗

A novel arrangement of zinc-binding residues and secondary structure in the C3HC4 motif of an alpha herpes virus protein family.

A highly conserved, cysteine-rich region plays a crucial role in the function of a family of regulatory proteins encoded by alpha herpes viruses. The so-called C3HC4 motif spans approximately 60 residues and has been predicted to bind zinc. This motif occurs in a number of other viral and cellular proteins, many of which appear to be involved in some aspect of the regulation of gene expression. We have cloned and expressed in bacteria a portion of immediate-early protein Vmw110 of herpes simplex virus type 1 that encompasses the C3HC4 motif, and the equivalent regions from the homologous proteins of varicella zoster virus and equine herpes virus type 1 (EHV-1). All three polypeptides were purified and found to bind zinc stably. None of the three interacted significantly with either DNA or RNA under our assay conditions. The EHV-1 domain yielded interpretable proton nuclear magnetic resonance spectra. Assignment of resonances and analysis of nuclear Overhauser effects revealed its secondary structure. Starting from the N terminus, this consists of an ordered but irregular loop, the first two strands of a triple-stranded antiparallel beta-sheet, two turns of an alpha-helix, a second irregular loop, and the third strand of the beta-sheet. It appears that, taking the cysteine and histidine residues in turn, cysteine residues I, II, IV and V co-ordinate one zinc atom while the histidine residue and cysteine residues III, VI and VII co-ordinate a second zinc atom. This arrangement of secondary structure differs from that found in other characterized zinc-containing proteins.

Amino Acid Sequence↗

Acupuncture fails to improve treatment outcome in alcoholics.

Fifty-six alcoholics (49 male, 7 female) of lower socioeconomic class attending an outpatient treatment program in Brooklyn, New York were prospectively randomized to one of three treatment group: point-specific acupuncture, sham transdermal stimulation or standard care (control). One third of the subjects reported a history of drug use in addition to alcohol. Results in this small sample showed no significant differences in attendance at Alcoholics Anonymous meetings, number of outpatients sessions attended, number of weeks in either the study or in the outpatient program, number of persons completing treatment or in the number of relapses. It is therefore concluded that in this small racially mixed sample of urban outpatient alcoholics, fixed point-specific standardized acupuncture did not improve outcome. We caution against the routine use of this treatment until more randomized controlled trials demonstrate a beneficial effect.

Acupuncture Points↗

Why do people need self-esteem? Converging evidence that self-esteem serves an anxiety-buffering function.

Three studies were conducted to assess the proposition that self-esteem serves an anxiety-buffering function. In Study 1, it was hypothesized that raising self-esteem would reduce anxiety in response to vivid images of death. In support of this hypothesis, Ss who received positive personality feedback reported less anxiety in response to a video about death than did neutral feedback Ss. In Studies 2 and 3, it was hypothesized that increasing self-esteem would reduce anxiety among individuals anticipating painful shock. Consistent with this hypothesis, both success and positive personality feedback reduced Ss' physiological arousal in response to subsequent threat of shock. Thus, converging evidence of an anxiety-buffering function of self-esteem was obtained.

Adaptation, Psychological↗

Evidence for sulfite as an essential metabolite for human peripheral lymphocytes.

Sulfite has been identified as an essential metabolite by means of growth studies using a chemically-defined, protein-free medium for culture of human peripheral lymphocytes. Sulfite reduced the amount of cysteine required for optimum growth by at least four-fold. In some subjects, sulfite stimulated growth even in the presence of optimal amounts of cysteine indicating that lymphocytes of some individuals are unable to convert cysteine to sulfite in adequate amounts.

Cell Division↗

Evidence of codependency in women with an alcoholic parent: helping out Mr. Wrong.

A conceptualization of codependency and its development, which is based largely on the writings of Karen Horney, is presented. It is proposed that having learned to obtain approval and self-esteem by conforming to the demands of an exploitive person, women with alcoholic parents will continue to seek opportunities to help such people. On the basis of this analysis, it was hypothesized that women with alcoholic parents would be more helpful to an experimenter portrayed as exploitive than to one portrayed as nurturant; women with nonalcoholic parents were expected to exhibit the opposite pattern. The results strongly supported the existence of codependent behavior in the women with alcoholic parents. The implication of these findings and directions for future research were briefly discussed.

Adolescent↗

Daptomycin versus vancomycin treatment for Staphylococcus aureus bacteremia in a murine model.

Daptomycin (LY 146032), a new lipopeptide antimicrobial agent with activity against gram-positive bacteria, was compared to vancomycin in the treatment of staphylococcal bacteremia in a murine model. Two hundred and ninety-nine mice were inoculated with 1 x 10(8) bacteria by the tail vein, and treatment was begun 3 days later. Two dosage regimens of each drug were used: 10 mg/kg and 5 mg/kg administered every 12 h for 14 days. A control group received no therapy. Survival was determined 31 days after inoculation. There was no significant difference in survival in any of the four treatment groups. The survival in all treatment groups was significantly greater than in the control group. Serum levels of daptomycin remained longer in the therapeutic range than serum levels of vancomycin. In the murine model of staphylococcal disease, daptomycin treatment was as effective as treatment with vancomycin.

Animals↗