Composite indicators may not be helpful in comparing health authorities.
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Breast Neoplasms↗
Biomedical subjects
M Reilly
Publications and source records attributed to M Reilly.
Detection of viral superantigen-class II MHC interactions at the cell surface.
Mouse mammary tumor virus superantigens (vSAgs) must bind to class II MHC proteins to activate T cells. Although direct interaction of vSAgs with class II proteins has been demonstrated biochemically, the details of this interaction are largely unresolved. To facilitate the study of class II-vSAg interactions, a sensitive assay has been developed that can detect binding of vSAgs to class II proteins on the cell surface. The assay measures changes in vSAg surface expression upon enzymatic removal of a co-expressed glycan-phosphatidyl inositol-anchored form of the class II molecule IE(k). Because the vSAgs are synthesized as integral membrane proteins that undergo proteolytic processing, an event that is likely required to eliminate membrane tethering, the data provide further evidence that a proteolytic fragment of vSAg is bound to class II proteins on the cell surface. The assay was utilized to identify mutant vSAgs that either did not associate with IE(k) molecules, or did not undergo furin-dependent proteolytic processing. Class II protein binding was detected using vSAg7 mutants that lacked furin endoprotease recognition sites, and after expression of vSAg in furin-deficient cells. The data demonstrate that furin-mediated processing is not necessary for association of vSAg7 with class II proteins, supporting previous studies that have indicated a role for alternative endoproteases in vSAg activation. However, because class II interactions were also noted in the apparent absence of proteases that are known to activate vSAgs, the data suggest that yet other proteases may process vSAgs in a fashion that does not necessarily lead to activation of T cells.
Animals↗
Intercellular transfer of a soluble viral superantigen.
Mouse mammary tumor virus (MMTV) superantigens (vSAgs) can undergo intercellular transfer in vivo and in vitro such that a vSAg can be presented to T cells by major histocompatibility complex (MHC) class II proteins on antigen-presenting cells (APCs) that do not express the superantigen. This process may allow T-cell activation to occur prior to viral infection. Consistent with these findings, vSAg produced by Chinese hamster ovary (CHO) cells was readily transferred to class II IE and IA (H-2(k) and H-2(d)) proteins on a B-cell lymphoma or mouse splenocytes. Fixed class II-expressing acceptor cells were used to demonstrate that the vSAg, but not the class II proteins, underwent intercellular transfer, indicating that vSAg binding to class II MHC could occur directly at the cell surface. Intercellular transfer also occurred efficiently to splenocytes from endogenous retrovirus-free mice, indicating that other proviral proteins were not involved. Presentation of vSAg7 produced by a class II-negative, furin protease-deficient CHO variant (FD11) was unsuccessful, indicating that proteolytic processing was a requisite event and that proteolytic activity could not be provided by an endoprotease on the acceptor APC. Furthermore, vSAg presentation was effected using cell-free supernatant from class II-negative, vSAg-positive cells, indicating that a soluble molecule, most likely produced by proteolytic processing, was sufficient to stimulate T cells. Because the membrane-proximal endoproteolytic cleavage site in the vSAg (residues 68 to 71) was not necessary for intercellular transfer, the data support the notion that the carboxy-terminal endoproteolytic cleavage product is an active vSAg moiety.
Animals↗
7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol in muscle as indices of oxidative stress: response to ethanol dosage in rats.
BACKGROUND: Alcohol-induced muscle disease (AIMD) encompasses both acute and chronic lesions, and affected patients exhibit concomitant functional and structural lesions. The pathogenic mechanisms are unknown, although it is possible that defects in the membrane-lipid domain are involved. Therefore, the effect of acute ethanol on membrane lipid from rat skeletal muscles (control, n = 7; ethanol, n = 7) was investigated. METHODS: Soleus and plantaris skeletal muscles were collected 24 hr after a single dose of 75 mmol/kg of ethanol. Lipids were analyzed by high-performance liquid chromatography with postcolumn chemiluminescence. RESULTS: We found that two cholesterol-derived hydroperoxides, 7alpha-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH) and 7beta-hydroperoxycholest-5-en-3beta-ol (7beta-OOH) were present in soleus muscles of control animals (1.29 nmol/g and 3.20 nmol/g, respectively) and in plantaris (1.83 and 5.18 nmol/g, respectively). These hydroperoxides were significantly elevated by acute ethanol, in not only plantaris but also soleus skeletal muscle of rats. In contrast, protein carbonyl concentration, another indicator of oxidative stress, albeit to proteins, was not significantly affected in either soleus or plantaris muscles of ethanol dosed rats. In addition, gas chromatographic study of fatty acid composition from phospholipid of rat muscle showed a significant increase of 18:2 by ethanol in plantaris as well as soleus. Concomitant decreases occurred in the nonessential/essential fatty acid ratios. CONCLUSIONS: This is the first report on 7alpha-OOH and 7beta-OOH accumulation in rat skeletal muscle, and it seems to reflect greater oxidative stress in the pathology of muscle of rats treated with acute ethanol. Together with the elevation of 18:2, these results signify perturbations in membrane lipids in response to ethanol, which may have important implications for the pathogenesis of alcohol-induced muscle disorders.
Animals↗
Trauma in the very elderly: A community-based study of outcomes at trauma and non-trauma centers
Published in: Acad Emerg Med. 2000; 7: 568.
Journal Article↗
Secondary prevention following fractured neck of femur: a survey of orthopaedic surgeons practice.
Fractured neck of femur is one of the most common reasons for hospital admission in the elderly population. Despite this little attention is given to the area of secondary prevention. To assess the variation in clinical practice among orthopaedic surgeons with regard to the use of secondary preventive measures in relation to fractured neck of femur. A postal survey using a self-completed questionnaire among all orthopaedic surgeons throughout the Republic of Ireland. The study questionnaire addressed unit information prophylaxis for deep venous thrombosis and investigation and secondary prevention of fractured neck of femur. It gave a clinical scenario of a 72-year old female who was admitted with a fractured neck of femur after a minor fall. A reminder was sent to the non-responders. Data were analysed using chi-squared test. The number of completed questionnaires returned was 89 giving a response rate of 66%. Of these 71(82.6%) reported that they would not initiate or recommend investigation of the extent of the underlying osteoporosis in the specific case upon which the questionnaire was based. With regard to the issue of secondary prevention 16(18%) stated that they would prescribe Vitamin D and 26(29%) would prescribe calcium supplements. 15(17%) would use bisphosphonates and 15(17%) would prescribe hormone replacement therapy. Only one respondent would use an external hip protector. There is an underuse of secondary preventive measures with regard to fractured neck of femur. There needs to be clear definition of roles and perhaps the development of agreed local protocols in order that patients with hip fractures do not miss out on potentially beneficial treatment. There is an underuse of secondary preventive measures with regard to fractured neck of femur. There needs to be clear definition of roles and perhaps the development of agreed local protocols in order that patients with hip fractures do not miss out on potentially beneficial treatment.
Aged↗
Carbonyl levels in type I and II fiber-rich muscles and their response to chronic ethanol feeding in vivo and hydroxyl and superoxide radicals in vitro.
BACKGROUND: Chronic alcoholic myopathy is characterized by selective reductions in the size of Type II skeletal muscle fibers (i.e., glycolytic, anaerobic fast-twitch). Type I (i.e., oxidative, aerobic, slow twitch) fibers are relatively resistant. It is possible that reactive oxygen species may preferentially damage the Type II fibers because the concentrations of several antioxidant enzymes are lower in Type II compared with Type I fibers. METHODS: To test the hypothesis, we measured protein carbonyl levels in Type I (i.e., soleus) and Type II (i.e., plantaris) fiber-rich muscles of rats subjected to chronic alcohol dosage with the Lieber-DeCarli regimen. Muscles were also exposed to hydroxyl or superoxide radicals in vitro. RESULTS: The Type I fiber-predominant soleus of control animals had less carbonyl than the Type II fiber-predominant plantaris. In rats that were fed ethanol for 6 weeks, the weights of the plantaris muscle were preferentially reduced but changes in soleus weight did not achieve significance. However, carbonyl levels were not significantly altered in any muscle in response to alcohol feeding. Calculation of the data in terms of total carbonyl per whole muscle showed decreases in both soleus and plantaris at the end of the 6-week alcohol feeding period. In response to hydroxyl radical (OH*) generation in vitro, protein carbonyl increased substantially in both soleus and plantaris muscles, but more so in the soleus. The increase in carbonyl in control soleus muscles in response to OH* was significantly lower than in soleus muscles from alcohol-fed animals. The increase in control plantaris muscle was not significantly different from the increase in carbonyl in corresponding muscles from ethanol-fed rats in response to OH*. In response to superoxide radicals, carbonyl in control soleus increased, an effect similar to that recorded in the soleus from ethanol-fed rats. In control plantaris, carbonyl increased in response to superoxide radicals, an effect not significantly different to the increase in plantaris from alcohol-fed rats. CONCLUSIONS: Using increased carbonyl concentrations as an indicator of muscle damage by reactive oxygen species, we concluded (1) there is no evidence of enhanced reactive oxygen species-induced damage to mixed muscle proteins in either Type I or Type II muscles in response to alcohol feeding; (2) Type II muscles have a greater capacity than Type I muscles to protect against damage (as indicated by carbonyl formation) by both hydroxyl and superoxide radicals in vitro; (3) alcohol reduces the capacity of Type I muscle to resist hydroxyl radical-induced protein damage, a mechanism that may arise through impairment of other antioxidant systems or other process not yet elucidated.
Alcoholism↗
Quantitative high performance liquid chromatography/tandem mass spectrometric analysis of the four classes of F(2)-isoprostanes in human urine.
Isoprostanes (iPs) are free radical catalyzed prostaglandin isomers. Analysis of individual isomers of PGF(2alpha)-F(2)-iPs-in urine has reflected lipid peroxidation in humans. However, up to 64 F(2)-iPs may be formed, and it is unknown whether coordinate generation, disposition, and excretion of F(2)-iPs occurs in humans. To address this issue, we developed methods to measure individual members of the four structural classes of F(2)-iPs, using liquid chromatography/tandem mass spectrometry (LC/MS/MS), in which sample preparation is minimized. Authentic standards of F(2)-iPs of classes III, IV, V, and VI were used to identify class-specific ions for multiple reaction monitoring. Using iPF(2alpha)-VI as a model compound, we demonstrated the reproducibility of the assay in human urine. Urinary levels of all F(2)-iPs measured were elevated in patients with familial hypercholesterolemia. However, only three of eight F(2)-iPs were elevated in patients with congestive heart failure, compared with controls. Paired analyses by GC/MS and LC/MS/MS of iPF(2alpha)-VI in hypercholesterolemia and of 8, 12-iso-iPF(2alpha)-VI in congestive heart failure were highly correlated. This approach will permit high throughput analysis of multiple iPs in human disease.
Adolescent↗
Risk of HIV infection in oral contraceptive pill users: a meta-analysis.
OBJECTIVE: To review the literature and present a summary estimate of the association between HIV-1 acquisition or HIV-1 serostatus and oral contraceptives. DATA SOURCES: MEDLINE database (January 1986-October 1997), AIDSLINE database (January 1980-October 1997), bibliographies of identified articles, and experts in the field of heterosexual HIV transmission. STUDY SELECTION: In all, 591 articles were examined. Twenty-eight studies provided adequate data to calculate a risk estimate for the association of HIV-1 serostatus or HIV-1 seroconversion with oral contraceptives and were selected for inclusion. RESULTS: The overall summary odds ratio (OR) for the association between seroprevalent or seroincident HIV-1 infection and use of oral contraceptives in the 28 studies was 1.19 (95% confidence interval [CI], 0.99-1.42). The summary OR for 21 cross-sectional studies was 1.21 (95% CI, 1.01-1.44), whereas the summary relative risk for seven prospective studies was 1.32 (95% CI, 1.12-1.57). Study quality was assessed by applying a scale reflecting study design, measurement of exposure, ability to assess confounding, and publication status. The summary OR for the eight best studies was 1.60 (95% CI, 1.05-2.44). When analysis was limited to studies conducted in Africa, the summary OR was 1.45 (95% CI, 1.15-1.83) for the 14 studies overall, and 1.65 (95% CI, 1.09-2.52) for the seven best studies. CONCLUSION: This meta-analysis found a significant association between oral contraceptive use and HIV-1 seroprevalence or seroincidence. For women at risk of HIV-1 infection, oral contraceptive use for prevention of pregnancy should be accompanied by condom use for prevention of HIV-1 infection.
Confounding Factors, Epidemiologic↗
Effects of human immunodeficiency virus 1 infection on microbial origins of pelvic inflammatory disease and on efficacy of ambulatory oral therapy.
OBJECTIVE: This study was undertaken to determine the effects of human immunodeficiency virus 1 infection on the clinical presentation, severity, causal organisms, and response to ambulatory therapy of pelvic inflammatory disease. STUDY DESIGN: Women 18 to 40 years old with lower abdominal pain for <1 month were recruited. Participants underwent a standardized questionnaire, physical examination, screening for human immunodeficiency virus 1 and other sexually transmitted infections, and endometrial biopsy to detect plasma cell endometritis. Reevaluations were performed at 1 and 4 weeks to assess response to therapy. RESULTS: Among 162 women with adequate endometrial biopsy specimens 63 (39%) had histologically confirmed endometritis. Endometritis was more frequent among women who were seropositive for human immunodeficiency virus 1 than among women who were seronegative (odds ratio, 3.0; 95% confidence interval, 1.5-5.9). Infections with either Neisseria gonorrhoeae or Chlamydia trachomatis, or both, were least common and bacterial vaginosis was most common among human immunodeficiency virus 1-infected women with CD4 T-lymphocyte counts <400 cells/microL (P <. 04, P <.03, respectively). After oral antibiotic therapy, similar proportions of both women who were seropositive and women who were seronegative for human immuno-deficiency virus 1 had a >/=75% reduction in clinical severity score (81% vs 86%). CONCLUSION: Outpatient treatment of pelvic inflammatory disease was successful regardless of human immunodeficiency virus 1 serostatus.
Administration, Oral↗
A likelihood-based method of identifying contaminated lots of blood product.
BACKGROUND: In 1994 a small cluster of hepatitis-C cases in Rhesus-negative women in Ireland prompted a nationwide screening programme for hepatitis-C antibodies in all anti-D recipients. A total of 55 386 women presented for screening and a history of exposure to anti-D was sought from all those testing positive and a sample of those testing negative. The resulting data comprised 620 antibody-positive and 1708 antibody-negative women with known exposure history, and interest was focused on using these data to estimate the infectivity of anti-D in the period 1970-1993. METHODS: Any exposure to anti-D provides an opportunity for infection, but the infection status at each exposure time is not observed. Instead, the available data from antibody testing only indicate whether at least one of the exposures resulted in infection. Using a simple Bernoulli model to describe the risk of infection in each year, the absence of information regarding which exposure(s) led to infection fits neatly into the framework of 'incomplete data'. Hence the expectation-maximization (EM) algorithm provides estimates of the infectiousness of anti-D in each of the 24 years studied. RESULTS: The analysis highlighted the 1977 anti-D as a source of infection, a fact which was confirmed by laboratory investigation. Other suspect batches were also identified, helping to direct the efforts of laboratory investigators. CONCLUSIONS: We have presented a method to estimate the risk of infection at each exposure time from multiple exposure data. The method can also be used to estimate transmission rates and the risk associated with different sources of infection in a range of infectious disease applications.
Algorithms↗
Branchial plexopathy related to alcohol intoxication.
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Aged↗
Incorporating music into the surgical environment.
Responsibility for patient comfort has always been the concern of the nurse. Conscious sedation and or local anesthesia are commonly becoming the primary method of anesthesia for a variety of outpatient plastic surgical procedures. These surgical methods require the nurse to become aware of nonchemical adjuncts that can assist in providing a safe comfortable atmosphere for the patients. Furthermore, many patients now request nonchemical adjuncts for anxiolysis and sedation as well as for analgesia in the surgical suite. This article will provide the nurse with a basic overview of one such alternative, music, including a brief historical review, relevant research, and guidelines for use of music with the operative client.
Choice Behavior↗
Perioperative considerations for patients with musculoskeletal and neuromuscular disorders.
This article first presents a brief description of musculoskeletal disease, then the anesthetic drugs that can trigger distress, and finally recommendations for perioperative nursing care based on pathophysiology and preservation of strength and function. The administration of a variety of anesthetic agents can exacerbate symptoms or result in unpredictable untoward effects on patients with musculoskeletal disease. Neuromuscular diseases result in diminished muscle strength. These deviations in structure and function must be considered when drafting a successful plan of care.
Humans↗
Redundant proteolytic activation of a viral superantigen.
Proteolytic activation of viral superantigens (vSAgs)4 expressed in Chinese hamster ovary (CHO) cells is required for T cell stimulation, and is mediated primarily by the protein convertase (PC) furin. Three PC recognition sites are highly conserved in vSAgs, but it was not known which sites are required for PC dependent vSAg activation. Moreover, because the PC recognition sites are not conserved in all functional vSAgs it was possible that activation could occur by processing at any of several sites. To identify the location(s) where processing of vSAg7 generates an active superantigen, each of two PC recognition sites, and a third related site were altered by in vitro mutagenesis, and the mutant proteins were tested for their abilities to activate T cells. Mutation of the PC recognition site at position 68-71 in vSAg7 had no effect on its ability to activate T cells. Mutation of the processing site at position 169-172 completely abolished T cell activation, and indicated that cleavage at this position was obligatory for proteolytic activation of vSAg7. However, introduction of a PC recognition site at position 192-195, a position that in many other vSAgs encodes a PC recognition site, restored activity to a vSAg7 protein that lacked a recognition site at position 169-172. The data revealed that processing of vSAgs at either position 169-172 or 192-195 was sufficient for vSAg7 activation, and explain how vSAgs that lack some PC recognition sites can be activated by proteolytic processing.
Animals↗
Effect of human immunodeficiency virus type 1 infection upon acute salpingitis: a laparoscopic study.
To determine the effect of human immunodeficiency virus type 1 (HIV-1) infection upon pelvic inflammatory disease (PID), a laparoscopic study of acute PID was conducted in Nairobi, Kenya. Subjects underwent diagnostic laparoscopy, HIV-1 serology, and testing for sexually transmitted diseases. Of the 133 women with laparoscopically verified salpingitis, 52 (39%) were HIV-1-seropositive. Tubo-ovarian abscesses (TOA) were found in 33% of HIV-1-infected and 15% of HIV-1-uninfected women (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.5). Among seropositive women, TOA was found in 55% of those with CD4 cell percent <14% vs. 28% with CD4 cell percent>14% (OR 3.1, 95% CI 0.6-15.3). Neisseria gonorrhoeae was detected in 37 women (28%) and Chlamydia trachomatis in 12 (9%); neither was significantly related to HIV-1 seropositivity. Length of hospitalization was not affected by HIV-1 serostatus overall but was prolonged among HIV-1-infected women with CD4 cell percent <14%. Among patients with acute salpingitis, likelihood of TOA was related to HIV-1 infection and advanced immunosuppression. In general, HIV-1-seropositive women with acute salpingitis responded well to treatment.
Abscess↗
Cervical and vaginal shedding of human immunodeficiency virus type 1-infected cells throughout the menstrual cycle.
Cervical and vaginal secretions from 17 women infected with human immunodeficiency virus type 1 (HIV-1) were evaluated daily through the course of one menstrual cycle for HIV-1 DNA (21-31 visits per woman). HIV-1-infected cells were detected in 207 (46%) of 450 endocervical swabs and 74 (16%) of 449 vaginal swabs. There was considerable variability in the percentage of positive swabs from each woman, ranging from 4% to 100% of endocervical swabs and from 0 to 71% of vaginal swabs. In multivariate analyses, plasma HIV-1 RNA was significantly associated with shedding of HIV-1-infected cells; each 1-unit increase in the log of plasma virus load was associated with a 5.6-fold increase in the odds of cervical shedding (95% confidence interval [CI], 2.1-14.8) and a 3.9-fold increase in the odds of vaginal shedding (95% CI, 2.1-7.2). There was no discernible pattern of genital tract shedding with phase of the menstrual cycle and no significant association with serum estradiol or progesterone levels.
Adult↗
Response persistence under ratio and interval reinforcement schedules.
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Journal Article↗