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Biomedical subjects

M Elliott

Publications and source records attributed to M Elliott.

At least 37 records · Page 2Linked to original sources
PubMed1997

Repeatability and accuracy of automated refraction: a comparison of the Nikon NRK-8000, the Nidek AR-1000, and subjective refraction.

This study assessed the repeatability of the Nikon NRK-8000, the Nidek AR-1000, and subjective refraction. In addition, the accuracy of the Nikon and the Nidek were evaluated in comparison to subjective refraction. Measurements were taken with all 3 techniques on 2 separate occasions with a test-retest separation of at least 24 h. The right eyes of 30 normal subjects were used. Repeatability and accuracy statistics and plots were generated using matrix representations of dioptric power. Subjective refraction was the most repeatable method, with the coefficient of repeatability (COR) found to be 0.611, 0.224, and 0.490 in the vertical, torsional, and horizontal meridians. The autorefractors' COR was found to range from 0.712 to 0.826 for the vertical and horizontal meridians, whereas the torsional meridian ranged from 0.224 to 0.319.

Adult↗
PubMed1997

TNF blockade in rheumatoid arthritis: implications for therapy and pathogenesis.

The role of the immune response in rheumatoid arthritis (RA) is a subject of debate, although it is widely believed to be a T-cell-driven disease. Progress is being hindered by lack of convincing evidence of a defined specific antigen initiating or perpetuating the response. Clinical trials using monoclonal antibodies directed against T-cell surface molecules such as CD4. CD5, and CD7 have thus far not provided evidence of efficacy. The negative data may reflect inadequate dosing or could suggest that indiscriminate depletion of T cells is insufficient by itself as a therapeutic strategy. Blocking proinflammatory cytokines (e.g. TNF alpha, IL-1) or augmenting anti-inflammatory cytokines (e.g. IL-10) offers an alternative approach to therapy. Clinical trials using monoclonal anti-TNF alpha have been particularly successful in controlling inflammation and markedly reducing acute phase proteins and cellular ingress. However, because disease invariably relapses, repeated therapy is necessary. Preliminary experience suggests that this is possible. Anti-TNF therapy for RA has defined a molecular target and new approach for treating immuno-inflammatory disorders.

Animals↗
PubMed1997

Regulation of heme biosynthesis in Salmonella typhimurium: activity of glutamyl-tRNA reductase (HemA) is greatly elevated during heme limitation by a mechanism which increases abundance of the protein.

In Salmonella typhimurium and Escherichia coli, the hemA gene encodes the enzyme glutamyl-tRNA reductase, which catalyzes the first committed step in heme biosynthesis. We report that when heme limitation is imposed on cultures of S. typhimurium, glutamyl-tRNA reductase (HemA) enzyme activity is increased 10- to 25-fold. Heme limitation was achieved by a complete starvation for heme in hemB, hemE, and hemH mutants or during exponential growth of a hemL mutant in the absence of heme supplementation. Equivalent results were obtained by both methods. To determine the basis for this induction, we developed a panel of monoclonal antibodies reactive with HemA, which can detect the small amount of protein present in a wild-type strain. Western blot (immunoblot) analysis with these antibodies reveals that the increase in HemA enzyme activity during heme limitation is mediated by an increase in the abundance of the HemA protein. Increased HemA protein levels were also observed in heme-limited cells of a hemL mutant in two different E. coli backgrounds, suggesting that the observed regulation is conserved between E. coli and S. typhimurium. In S. typhimurium, the increase in HemA enzyme and protein levels was accompanied by a minimal (less than twofold) increase in the expression of hemA-lac operon fusions; thus HemA regulation is mediated either at a posttranscriptional step or through modulation of protein stability.

Acclimatization↗
PubMed1997

Investigation of the association between the presence of cytoplasmic residues on the human sperm midpiece and defective sperm function.

Defective sperm function has been identified as one of the most common causes of human infertility. The aim of this investigation was to identify whether the presence of retained cytoplasm on the human sperm midpiece is associated with defective sperm function. Statistical analysis of data demonstrated a strong negative correlation between the presence of residual cytoplasm on the midpiece of spermatozoa in the inseminate and fertilization rate during IVF. Significant negative correlations were also identified between the percentage of spermatozoa in the ejaculate bearing cytoplasmic residues and (i) spermatozoa having membrane integrity and (ii) sperm concentration. A highly significant positive correlation was also revealed between the percentage of spermatozoa in the ejaculate with membrane integrity and the percentage of motile spermatozoa. These correlations suggest that retained cytoplasm is a cause of subfertility. Measurements of the percentage of spermatozoa bearing residual cytoplasm in the IVF inseminate could provide the basis for a simple predictive test before IVF.

Cytoplasm↗
PubMed1996

Understanding the conflicts of patient empowerment.

In line with the emphasis placed by nursing development units on critical scrutiny and practice evaluation, the authors review the patient empowerment nursing literature to identify its practical implications for their clinical area and staff. This article presents some early conclusions arising out of this process and highlights the conflicts which nurses face in ensuring that patients are empowered while maintaining their rights and privacy.

Conflict, Psychological↗
PubMed1996

Effects of inhibition of complement activation using recombinant soluble complement receptor 1 on neutrophil CD11b/CD18 and L-selectin expression and release of interleukin-8 and elastase in simulated cardiopulmonary bypass.

The inflammatory response to cardiopulmonary bypass includes activation of complement and induction of several neutrophil activation pathways. A recombinant soluble form of complement receptor 1 was used as a specific inhibitor of complement activation in simulated cardiopulmonary bypass circuits. Substantial complement activation was observed in these circuits with progressive accumulation of both plasma C3a and terminal complement complex. Soluble complement receptor 1 resulted in a significant reduction in C3a levels (p < 0.01) but did not inhibit terminal complement complex generation. A marked rise in neutrophil CD11b/CD18 expression, simultaneous loss of L-selectin expression, and a progressive accumulation of plasma elastase-alpha 1-antitrypsin occurred and were not affected by soluble complement receptor. However, generation of interleukin-8 in the circuits was inhibited (p < 0.05) by pretreatment with soluble complement receptor. These data suggest that changes in neutrophil activation seen during cardiopulmonary bypass may not be induced directly by anaphylatoxin generation.

CD11 Antigens↗
PubMed1996

Intracardiac repair of lesions associated with atrioventricular discordance.

OBJECTIVE: Discordant atrioventricular (AV) connection is a rare congenital cardiac anomaly. Associated cardiac defects modify the physiology, clinical presentation, and surgical management of these patients. We have reviewed our overall experience with 90 patients operated for lesions associated with AV discordance between 1975-1990. METHODS: 90 patients, consecutively operated between 1975-1990, were reviewed. Patients' charts, angiograms and echocardiograms were studied. Follow-up was obtained from our records or was requested from referring cardiologists/paediatricians. It was completed in December 1992. For the analysis of risk factors of early death we used P values by chi-squared and Fisher's exact test. For the analysis of the triangulated events, we used the Kaplan-Meier method. Variables associated with P value over 0.20 were eliminated. RESULTS: 90 patients aged 6 months-30 years (mean 9.1 year) underwent repair of cardiac anomalies associated with AV discordance. Three patients had total cavopulmonary connection; the remainder received biventricular repair. Most important associated malformations were ventricular septal defect (77), subpulmonary obstruction (68) and tricuspid valve anomaly (21). 59 patients received extracardiac valved conduit, 10 had tricuspid valve replacement. Thirteen patients died in hospital (14%). One year and 10 year actuarial survival rate was 84% and 70% respectively. The most significant factors for early death were: anatomically abnormal tricuspid valve (P < 0.0001), tricuspid valve regurgitation (P < 0.002), date of operation (P < 0.012), preoperative or perioperative complete heart block (P < 0.015), and tricuspid valve surgery (P < 0.05). Complete heart block developed in 17 (20%) out of 85 patients who did not have it preoperatively. During the follow-up, 22 intracardiac reoperations were necessary (4 died). 63 patients of 73 survivors (86%) remain in NYHA Class 1, 6 in Class 2 and 4 in Class 3. CONCLUSIONS: The operative mortality was 14%. Twenty per cent of patients developed complete heart block. These results improved in the later part of the series (1985-1990); mortality decreased to 5% and incidence of heart block to 14%. Cardiac anomalies associated with AV discordance still present a surgical challenge. The data reported in our study should serve as a useful baseline for evaluation of newer surgical techniques, such as the "double switch" operation.

Adolescent↗
PubMed1996

Closure of muscular ventricular septal defects through a left ventriculotomy.

OBJECTIVE: To evaluate the results of closure of muscular ventricular septal defects through a left thoracotomy. METHODS: Records of 23 children operated consecutively between 1972 and 1990 were studied. Age of patients was 2.8 +/- 3 years (2 months-10 years), weight 8.9 +/- 5.7 kg (2.6-22 kg). Ten patients (43%) had undergone one and 4 patients (17%) two previous cardiac operations. Late follow-up was obtained from direct examination of patients or from reports of their referring physicians. Bypass time was 89 +/- 28 min (66-167 min). The aorta was cross-clamped for 44 +/- 15 min (21-66 min). Until 1977 operations were performed with moderate hypothermia and intermittent aortic cross-clamping. After 1978 deep hypothermia (20-25 degrees C) and cold crystalloid cardioplegia was used. Ventricular septal defects not accessible from other approaches were closed through a small fish-mouth incision in the apex of the left ventricle. Patients' data were sampled and stored in a computerised database. Risk factors were evaluated by stepwise logistic regression. RESULTS: Four patients died in the hospital (17%); two died later. Two required reoperation for residual/recurrent defects. All patients, except two from abroad, were available for follow-up, which ranged from 36 months to 18 years (mean 11.3 years). All were in NYHA class I. Only two risk factors were identified: the number of ventricular septal defects (P < 0.05) and associated atrial septal defect (P < 0.02). Early echocardiographic evaluation showed good LV size and function in all except one patient, who had a perioperative septal infarction. Late echocardiography performed in six patients demonstrated normal LV shortening without evidence of regional wall abnormality. CONCLUSIONS: Left ventriculotomy is a useful approach for closure of low muscular ventricular septal defects in selected patients.

Cardiac Catheterization↗
PubMed1996

T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients.

The introduction and expression of genes in somatic cells is an innovative therapy for correcting genetic deficiency diseases and augmenting immune function. A potential obstacle to gene therapy is the elimination of such gene-modified cells by an immune response to novel protein products of the introduced genes. We are conducting an immunotherapy trial in which individuals seropositive for human immunodeficiency virus (HIV) receive CD8+ HIV-specific cytotoxic T cells modified by retroviral transduction to express a gene permitting positive and negative selection. However, five of six subjects developed cytotoxic T-lymphocyte responses specific for the novel protein and eliminated the transduced cytotoxic T cells. The rejection of genetically modified cells by these immunocompromised hosts suggests that strategies to render gene-modified cells less susceptible to host immune surveillance will be required for successful gene therapy of immunocompetent hosts.

Antigen Presentation↗
PubMed1996

Midazolam following open heart surgery in children: haemodynamic effects of a loading dose.

Our objective was to establish the safety and effectiveness of a loading dose of midazolam for postoperative sedation of children recovering from open heart surgery; a prospective randomized placebo-controlled double-blind study was done with subjects randomized to three groups according to loading dose. I = 0.08 mg.kg-1; II = 0.04 mg.kg-1; and III = 0.00 mg.kg-1 (placebo). An open label continuous midazolam infusion protocol followed. Haemodynamic parameters were monitored. The study was discontinued following an adverse event involving the 23rd subject. When data for all 23 subjects were combined, there was a mean decrease of 10% in blood pressure (BP) 30 min after the loading dose (P < 0.001). Heart rate change was less significant. Clinicians identified four hypotensive episodes as temporally associated with the midazolam load, two each in Groups I (0.08 mg.kg-1) and III (placebo). One subject in Group I (the 23rd) became hypotensive within five min of receiving the loading dose, had a difficult clinical course and died four weeks postoperatively. We cannot conclude that the loading dose of midazolam had any systematic haemodynamic effect in our study population. Although the clinical course of the 23rd subject suggests a subset of more susceptible children (those who receive opioid analgesia with midazolam, are volume-restricted, and/or undergo more complex forms of surgical correction), many critical care patients are inherently physiologically unstable, and concluding clinically that blood pressure fluctuation is drug related may be erroneous.

Blood Pressure↗
PubMed1996

Overexpression of Bcl-2 and mutations in p53 and K-ras in resected human non-small cell lung cancers.

We investigated expression of Bcl-2, mutations in p53, and K-ras oncogene in 51 resected human non-small cell lung cancers. The studies were designed to test for the possibility of cooperativity between these oncogenes and p53 in the pathogenesis of lung cancer. An inverse relationship was found between expression of Bcl-2 and mutant p53 by immunohistochemistry (P < 0.01; Fisher exact test), suggesting that either Bcl-2 overexpression or mutations in p53 may fulfill a critical function in the pathogenesis of human non-small cell lung cancers. Tumors that harbored K-ras codon 12 mutations seldom had p53 mutations or overexpressed Bcl-2. Statistical analysis of these data showed that mutations in p53 and K-ras or overexpression of Bcl-2 and mutations in K-ras occurred at a frequency that could be explained only by chance [P > 0.1 in each case (Fisher exact tests)]. This suggests that cooperativity between mutant K-ras and mutant p53 or mutant K-ras and overexpressed Bcl-2 is not a common mechanism in the pathogenesis of human non-small cell lung cancers.

Adenocarcinoma↗
PubMed1995

Separation of sequence requirements for HSV-1 Vmw110 multimerisation and interaction with a 135-kDa cellular protein.

Herpes simplex virus type 1 immediate-early polypeptide Vmw110 (ICP0) is a general transactivator of gene expression in transfection assays and is required for the fully efficient onset of viral lytic replication. It has also been implicated in the process of viral reactivation from latency. Its mechanism of action is unknown, but any involvement in latency requires interactions between viral and host factors. We have previously shown that Vmw110 binds to a 135-kDa cellular protein. In this paper we define a short region towards the C-terminal end of Vmw110 that is required for the 135-kDa protein interaction in virus-infected cells and in vitro. We also confirm that the C-terminal region of Vmw110 contains residues that are responsible for the multimerisation of the protein; these sequences are at least partially distinct from those involved in 135-kDa binding. Both multimerisation and 135-kDa protein interaction are required for full viral infectivity, and elimination of these functions affects the normal interactions between Vmw110 and cellular nuclear structures that contain the PML protein.

Animals↗
PubMed1995

Moloney leukemia virus-induced cell surface antigen mimicry by monoclonal antibodies.

We have investigated antigen-independent modulation of immune responses by monoclonal antibodies directed against both viral and nonviral antigens. BALB/c mice were immunized with monoclonal IgM (i.e. Ab1) specific for either Moloney murine leukemia virus-induced cell surface antigen (MCSA) or the hapten 2,4-dinitrophenyl (DNP). Injection with either Ab1 activated a functional idiotypic (Id) network as evidenced by production of both anti-Id (Ab2) antibodies and anti-anti-Id (Ab3) antibodies. A subset of induced Ab3 (designated Ab1'), exhibited specificity for antigen (virus or DNP). In mice immunized with anti-Id antibodies (Ab2), production of Ab3 and Ab1' was also observed. In the MCSA system, antibody-induced Ab1' responses were effective in protecting mice from tumor development upon subsequent challenge with live virus. Furthermore, antigen-independent modulation of immunity to both viral and nonviral antigens was found to be thymus-dependent. Similar findings in other viral systems suggest that antibody-induced activation of Id networks may prove a viable alternative vaccine strategy that can elicit antigen-specific responses, and in some cases protection, in the apparent absence of exposure to antigen.

Animals↗
PubMed1995

Child sexual abuse prevention: what offenders tell us.

Ninety-one child sex offenders were interviewed about the methods they used to target children, the age range of their victims, how they selected children and maintained them as victims, and what suggestions they had for preventing child sexual abuse. Offenders were selected from treatment programs, probation, special hospitals, and prisons. They were interviewed using a semi-structured questionnaire. Results indicate that offenders gained access to children through caretaking, such as babysitting; targeted children by using bribes, gifts and games; used force, anger, threats, and bribes to ensure their continuing compliance; and systematically desensitized children through touch, talk about sex, and persuasion. Nearly half the offenders had no bad feelings about sexually abusing children. The implications for prevention programs are discussed.

Adolescent↗
PubMed1995

Comparisons of risk factors for HIV-1 infection in Jefferson and Mobile County, Alabama.

A study of the Alabama state AIDS database was conducted to determine whether differences exist in demographic and risk characteristics between patients with HIV-1 in Jefferson and Mobile County. The authors found that the age distribution of patients with HIV-1, the percent of those having AIDS, and the percent of those surviving were very similar. However, significant differences existed in patient-reported risk factors in the two counties. Homosexuality was reported as the major risk factor in both counties. However, there was proportionately more homosexuality reported in Jefferson County and, conversely, more heterosexuality reported in Mobile. There also were significant differences in race and gender distributions in the two counties. This was due in part to the proportionately higher prevalence of African American females of reproductive age with HIV-1 in Mobile County. This may pose a significantly greater risk for pediatric AIDS among African American females in Mobile County.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The cellular RING finger protein PML is not a functional counterpart of the herpes simplex virus type 1 RING finger protein Vmw110.

Herpes simplex virus type 1 (HSV-1) immediate early protein Vmw110 (also known as ICP0) is required for the fully efficient expression of viral genes during onset of lytic growth and for normal reactivation from latency. Both Vmw110 and the cellular protein PML are members of the RING finger family of zinc binding domain proteins, a family which includes an increasing number of examples from a wide evolutionary range. The function of the RING finger domain is unknown, and the question arises whether the RING finger (like several other examples of conserved domains) fulfils similar functions in these diverse proteins. Another link between Vmw110 and PML is that at early times of HSV-1 infection Vmw110 migrates to distinct nuclear structures which contain the PML protein. In order to test the possibility that PML and Vmw110, or their RING finger domains, fulfill similar functions, we have constructed recombinant viruses that express either intact PML, or a chimeric Vmw110 protein which contains the PML RING finger in place of its own. The results indicate that the PML and Vmw110 RING fingers are not functionally interchangeable, and that PML is not a cellular functional counterpart of Vmw110.

Animals↗