Apoptosis: definition, mechanisms, and relevance to disease.
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Apoptosis↗
Biomedical subjects
M Denton
Publications and source records attributed to M Denton.
Gender differences in structural and behavioral determinants of health: an analysis of the social production of health.
This paper explores aspects of the social production of health by focussing on the ways in which levels of health are shaped by structures of social inequality and behaviors or 'lifestyles'. We address two questions: What is the relative importance of the social, structural and behavioral determinants of health? And, are there gender differences in the determinants of health? These questions are explored using multiple regression analyses of data from the 1994 Canadian National Population Health Survey. Two measures of health are used: subjective health status and the Health Utilities Index (a measure of functional health status). By structural determinants we refer to age, family structure, main activity, education, occupation, income and social support. Behavioral determinants include lifestyle factors related to smoking, drinking, weight and physical activity. Findings indicate that the structures of social inequality are the most important determinants of health acting both independently and through their influence on the behavioral determinants of health. There are very real differences in the factors that predict women's and men's health. For women, social structural factors appear to play a more important role in determining health. Being in the highest income category, working full-time and caring for a family and having social support are more important predictors of good health for women than men. Smoking and alcohol consumption are more important determinants of health status for men than women, while body weight and being physically inactive are more important for women than men. Our findings suggest the value of models which include a wide range of structural and behavioral variables and affirm the importance of looking more closely at gender differences in the determinants of health.
Alcohol Drinking↗
Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa.
Inherited retinal diseases are a common cause of visual impairment in children and young adults, often resulting in severe loss of vision in later life. The most frequent form of inherited retinopathy is retinitis pigmentosa (RP), with an approximate incidence of 1 in 3,500 individuals worldwide. RP is characterized by night blindness and progressive degeneration of the midperipheral retina, accompanied by bone spicule-like pigmentary deposits and a reduced or absent electroretinogram (ERG). The disease process culminates in severe reduction of visual fields or blindness. RP is genetically heterogeneous, with autosomal dominant, autosomal recessive and X-linked forms. Here we have identified two mutations in a novel retina-specific gene from chromosome 8q that cause the RP1 form of autosomal dominant RP in three unrelated families. The protein encoded by this gene is 2,156 amino acids and its function is currently unknown, although the amino terminus has similarity to that of the doublecortin protein, whose gene (DCX) has been implicated in lissencephaly in humans. Two families have a nonsense mutation in codon 677 of this gene (Arg677stop), whereas the third family has a nonsense mutation in codon 679 (Gln679stop). In one family, two individuals homozygous for the mutant gene have more severe retinal disease compared with heterozygotes.
Adult↗
Correlation between genotype and beta-lactamases of clinical and environmental strains of Stenotrophomonas maltophilia.
Heterogeneity of beta-lactamase production by 17 clinical and nine environmental isolates of Stenotrophomonas maltophilia was investigated using MICs of six different beta-lactam antibiotics, isoelectric focusing (IEF) and pulsed field gel electrophoresis. There was no clear correlation between the results of IEF, genotype and MIC determination. Environmental isolates were more susceptible than clinical isolates; eight clinical and none of the environmental isolates expressed high-level resistance to meropenem. Only two isolates expressed high-level resistance to ceftazidime. These results indicate that further studies are required to elucidate the extent of genetic heterogeneity within the L1 and L2 beta-lactamase genes.
Anti-Bacterial Agents↗
Histone acetyltransferase and protein kinase activities copurify with a putative Xenopus RNA polymerase I holoenzyme self-sufficient for promoter-dependent transcription.
Mounting evidence suggests that eukaryotic RNA polymerases preassociate with multiple transcription factors in the absence of DNA, forming RNA polymerase holoenzyme complexes. We have purified an apparent RNA polymerase I (Pol I) holoenzyme from Xenopus laevis cells by sequential chromatography on five columns: DEAE-Sepharose, Biorex 70, Sephacryl S300, Mono Q, and DNA-cellulose. Single fractions from every column programmed accurate promoter-dependent transcription. Upon gel filtration chromatography, the Pol I holoenzyme elutes at a position overlapping the peak of Blue Dextran, suggesting a molecular mass in the range of approximately 2 MDa. Consistent with its large mass, Coomassie blue-stained sodium dodecyl sulfate-polyacrylamide gels reveal approximately 55 proteins in fractions purified to near homogeneity. Western blotting shows that TATA-binding protein precisely copurifies with holoenzyme activity, whereas the abundant Pol I transactivator upstream binding factor does not. Also copurifying with the holoenzyme are casein kinase II and a histone acetyltransferase activity with a substrate preference for histone H3. These results extend to Pol I the suggestion that signal transduction and chromatin-modifying activities are associated with eukaryotic RNA polymerases.
Acetyltransferases↗
Acute bronchopulmonary infection due to Streptococcus milleri in a child with cystic fibrosis.
An 8 year old girl with cystic fibrosis had severe respiratory disease associated with chronic Pseudomonas aeruginosa bronchopulmonary infection. Despite regular courses of intravenous antipseudomonal antibiotics, she continued to deteriorate over 18 months with persistent productive cough, worsening respiratory function, and increasing oxygen dependence. During her 11th admission Streptococcus milleri was isolated from sputum cultures in addition to P aeruginosa. She failed to respond to antipseudomonal antibiotics but improved dramatically with the addition of intravenous benzylpenicillin. Although S milleri is considered a normal mouth commensal and its isolation from sputum of cystic fibrosis patients is of uncertain significance, it was associated with clinically significant infection in this child. S milleri was eradicated with antibiotic treatment and clinical improvement has been maintained.
Acute Disease↗
Endovascular treatment of a posttraumatic femoral vein-profunda femoris artery fistula.
PURPOSE: To describe successful endovascular management of a posttraumatic arteriovenous fistula (AVF) when a covered stent is unavailable. METHODS AND RESULTS: An AVF developed between the profunda femoris and the femoral vein in a 59-year-old man undergoing a total hip revision procedure. No covered stent being available, a Dacron plug was inserted on top of scaffolding created by a conventional stent and embolization coils. Successful control of hemorrhage and resolution of the AVF was documented. Pulmonary embolization was avoided by using this scaffolding technique. CONCLUSIONS: Dacron can be used for occlusion of a medium-sized artery in an emergency situation in selected cases.
Angiography↗
Endovascular repair of an aortoenteric fistula in a high-risk patient.
PURPOSE: To describe the endovascular repair of an aortoenteric fistula in a high-risk patient. METHODS AND RESULTS: A Vanguard tube stent-graft was deployed at the upper anastomotic suture line of a secondary aortoenteric fistula, successfully sealing the communication between the aorta and the third part of the duodenum without occlusion of the renal arteries. CONCLUSIONS: Endovascular stent-graft repair of aortoenteric fistulae is possible, but further evaluation of this technique will determine its role in the management of this complication.
Aged↗
Immunomodulatory functions of low-molecular weight hyaluronate in an acute rat renal allograft rejection model.
Low molecular weight hyaluronate (LMW-HA) blocks interactions between T lymphocyte CD44 and hyaluronate (HA), a heteropolysaccharide that is expressed on the surface of endothelial cells and ubiquitously in the extracellular matrix. This study was undertaken to assess the ability of LMW-HA to modify the course of experimental acute renal allograft rejection. Lewis (LEW) rats were bilaterally nephrectomized and received an orthotopic, fully MHC-mismatched, Wistar-Furth (WF) kidney transplant. Animals received either no treatment, low doses of cyclosporin A (CsA) on days 0 to 5, LMW-HA on days 0 to 5, or CsA plus LMW-HA on days 0 to 5 after transplantation. With no treatment, CsA monotherapy, or HA monotherapy, animals rejected their allografts at a median of 15, 13, and 7.5 d, respectively (P = NS). In contrast, combined CsA plus LMW-HA therapy prevented acute rejection and significantly prolonged graft survival (P = 0.008) to a median of 49.0 d. CsA/LMW-HA-treated grafts also demonstrated better preservation of renal function at day 30 (serum creatinine level, 1.38+/-0.8 mg/dl), compared with surviving animals treated with CsA alone (2.9+/-0.55 mg/dl, P<0.05). Histologic graft analysis of CsA/LMW-HA-treated animals at day 7 after transplantation showed minimal rejection and leukocyte infiltration, compared with all other groups. Intragraft gene expression analysis, using semiquantitative reverse transcription-PCR, at the same time point showed reductions of CD4, CD8, and interferon-gamma transcript levels in the combined-treatment group. This is the first study demonstrating the immunomodulatory functions of LMW-HA in vivo in the setting of organ transplantation. Defining the exact mechanisms that underlie this immunomodulation may provide the rationale to develop novel strategies for use in clinical transplantation.
Adjuvants, Immunologic↗
Inadequate control of lipid levels in patients with a previous myocardial infarction.
AIM: To access the current lipid management of late survivors of acute myocardial infarction. METHODS: A systematic follow-up of all survivors who had previously been screened for enrolment into one of three randomised clinical trials in Auckland was undertaken from December 1995 to January 1997. All contacted survivors were asked to answer a questionnaire regarding their current therapy and were invited to undergo venepuncture for a lipid assay. RESULTS: Of the 1036 patients with acute myocardial infarction screened for enrolment in the three trials there were 984 (95%) who survived 30 days. At a median of 5.5 years (interquartile range 3.2-8.5) follow-up, 641 (86%) survivors agreed to have a fasting lipid test. The mean total cholesterol level was 5.7 +/- 1.1 mmol/L high density lipoprotein cholesterol 1.1 +/- 0.3 mmol/L, low density lipoprotein cholesterol 3.8 +/- 0.9 mmol/L and triglyceride level 1.9 +/- 1.1 mmol/L. Two hundred and seven (32%) patients were treated with a lipid-modifying agent. Four hundred and forty-five (69%) patients had a cholesterol level > or = 5.2 mmol/L 381 (59%) patients had a level > or = 5.5 mmol/L and 72 (11%) patients had a level > or = 7.0 mmol/L of whom 62 patients were not being treated with a lipid-modifying agent. For the 107 patients with coronary artery bypass grafts, the mean cholesterol level was 5.4 mmol/L and the mean low density lipoprotein cholesterol level was 3.7 +/- 0.9 mmol/L, with 57 (53%) patients not being treated with a "statin" or "fibrate". CONCLUSION: Lipid management is suboptimal in this high risk population of patients post-infarction and greater efforts need to be made to achieve better control. Diet is frequently inadequate in these patients at high risk and statin therapy is indicated.
Aged↗
Two Indian siblings with Oguchi disease are homozygous for an arrestin mutation encoding premature termination.
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Adolescent↗
Functional popliteal entrapment syndrome.
BACKGROUND: Classic popliteal artery entrapment is caused by the abnormal relationship between the popliteal artery and the medial head of the gastrocnemius, resulting in repetitive arterial compression and trauma. There is, however, a distinct subset of calf claudicants who have an anatomically normal popliteal fossa but can occlude the popliteal artery by repetitive vigorous exercise which involves active plantar flexion with or without extension at the knee joint. METHODS: Eight patients who led a vigorous athletic lifestyle were evaluated with duplex scan and biplane angiogram after being referred for bilateral calf claudication. They were found to have significant stenosis or occlusion of the popliteal artery with active plantar flexion. All patients had transection of the medial head of the gastrocnemius muscle with release of any vascular bands tethering the popliteal artery. RESULTS: Seven of the eight patients had complete relief. One patient noticed return of claudication at long distances, but a postoperative angiogram was normal. In all patients postoperative duplex scan showed no stenosis or occlusion of the popliteal vessels with the foot in active plantar flexion and the knee in extension. CONCLUSIONS: Functional popliteal artery entrapment is becoming a significant cause of disabling claudication in young athletic individuals and needs to be diagnosed accurately for appropriate treatment. This condition is becoming well known with the incorporation of sports in the daily routine of most young people.
Adolescent↗
Microbiological and clinical aspects of infection associated with Stenotrophomonas maltophilia.
The gram-negative bacterium Stenotrophomonas maltophilia is increasingly recognized as an important cause of nosocomial infection. Infection occurs principally, but not exclusively, in debilitated and immunosuppressed individuals. Management of S. maltophilia-associated infection is problematic because many strains of the bacterium manifest resistance to multiple antibiotics. These difficulties are compounded by methodological problems in in vitro susceptibility testing for which there are, as yet, no formal guidelines. Despite its acknowledged importance as a nosocomial pathogen, little is known of the epidemiology of S. maltophilia, and although it is considered an environmental bacterium, its sources and reservoirs are often not readily apparent. Molecular typing systems may contribute to our knowledge of the epidemiology of S. maltophilia infection, thus allowing the development of strategies to interrupt the transmission of the bacterium in the hospital setting. Even less is known of pathogenic mechanisms and putative virulence factors involved in the natural history of S. maltophilia infection and this, coupled with difficulties in distinguishing colonization from true infection, has fostered the view that the bacterium is essentially nonpathogenic. This article aims to review the current taxonomic status of S. maltophilia, and it discusses the laboratory identification of the bacterium. The epidemiology of the organism is considered with particular reference to nosocomial outbreaks, several of which have been investigated by molecular typing techniques. Risk factors for acquisition of the bacterium are also reviewed, and the ever-expanding spectrum of clinical syndromes associated with S. maltophilia is surveyed. Antimicrobial resistance mechanisms, pitfalls in in vitro susceptibility testing, and therapy of S. maltophilia infections are also discussed.
Anti-Bacterial Agents↗
Molecular epidemiology of Stenotrophomonas maltophilia isolated from clinical specimens from patients with cystic fibrosis and associated environmental samples.
Stenotrophomonas maltophilia was isolated from the respiratory tracts of 41 (25%) of 163 children attending our pediatric cystic fibrosis unit between September 1993 and December 1995. The extents of S. maltophilia contamination of environmental sites frequented by these patients were investigated with a selective medium incorporating vancomycin, imipenem, and amphotericin B. Eighty-two isolates of S. maltophilia were cultured from 67 different environmental sites sampled between January and July 1996. The organism was widespread in the home environment, with 20 (36%) and 25 (42%) of sampled sites positive in the homes of colonized and noncolonized patients, respectively. In the nosocomial setting, it was isolated from 18 (32%) sites in the hospital ward and from 4 (17%) sites in the outpatient clinic area. The most common sites of contamination were sink drains, faucets, and other items frequently in contact with water. All environmental and clinical isolates were genotyped with enterobacterial repetitive intergenic consensus sequences as primers. A total of 33 of the 41 patients were colonized with unique strains, and four pairs of patients shared strains. Further characterization by pulsed-field gel electrophoresis after digestion with XbaI found that there was no evidence of patient-to-patient transmission; however, there was some evidence that a small number of patients may have acquired the organism from the hospital environment. Resampling of environmental sites in the hospital ward in January 1997 revealed evidence of genetic drift, complicating the accurate determination of environmental sources for clinical strains. The source of the majority of S. maltophilia strains colonizing the respiratory tracts of these patients with cystic fibrosis remained uncertain but may have represented multiple, independent acquisitions from a variety of environmental sites both within and outside the hospital.
Adolescent↗
Treatment of traumatic false aneurysm of the thoracic aorta with endoluminal grafts.
PURPOSE: Traumatic false aneurysms of the thoracic aorta presenting at a time remote from the original injury are a rare but complex problem. The treatment of a traumatic false aneurysm by endovascular techniques may offer many advantages over conventional open surgery. METHODS AND RESULTS: Two male patients presented with traumatic false aneurysm of the thoracic aorta after being treated emergently for visceral injuries from a gunshot wound in one and an automobile accident in the other. In both cases, the aneurysm was situated so that only the T11 intercostal artery would be sacrificed by endoluminal exclusion. Commercially available endoluminal stent-grafts (Talent) were deployed successfully. Recovery in both patients was rapid and uneventful with no neurological sequelae. Spiral computed tomographic scans at 1 year indicated sustained aneurysm exclusion and satisfactory endograft position. CONCLUSIONS: A customized endoluminal stent-graft can be used with great accuracy to exclude thoracic false aneurysms, avoiding the potential complexity and morbidity of an open thoracic approach.
Adult↗
Clinical practice guidelines: a tool to help provide quality care.
Significant variability of medical care exists in the United States that cannot be readily explained on the basis of severity of illness, patient demographics, or clinical necessity. One approach to promoting appropriate decision-making is to make the most recent and relevant information available to physicians in a practice guideline. Physicians are most likely to accept practice guidelines that address a specific need, are supported with scientific evidence, and offer the potential for improving patient outcomes. The implementation of a clinical practice guideline and its impact on the care of patients with uncontrolled hypertension are described.
Aged↗
Antimicrobial treatment of pulmonary colonization and infection by pseudomonas aeruginosa in cystic fibrosis patients.
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Anti-Bacterial Agents↗
Transcontinental importation into the UK of Escherichia coli expressing a plasmid-mediated AmpC-type beta-lactamase exposed during an outbreak of SHV-5 extended-spectrum beta-lactamase in a Leeds hospital.
Sixteen strains of Escherichia coli with high-level resistance to extended-spectrum cephalosporins and other classes of antibiotic have been isolated at St James' University Hospital, Leeds. They produce up to three separate beta-lactamases: TEM-1, SHV-5 and, in five isolates, a plasmid-mediated AmpC-type enzyme. With the exception of carbapenems, the isolates reported in this study were resistant to all beta-lactam antibiotics including extended-spectrum cephalosporins and the monobactam aztreonam. There was evidence of the spread of a plasmid encoding SHV-5, particularly amongst patients on the liver transplant unit. Sensitivity to beta-lactam antibiotics in five isolates expressing the AmpC-type beta-lactamase was not restored by the beta-lactamase inhibitor clavulanic acid. These bacteria also carried blaSHV-5 on a large plasmid. PCR-amplification of the structural gene and digestion with restriction endonucleases demonstrated that the plasmid-mediated blaAmpC probably identified as BIL-1 using the criteria available. Four of the five patients carrying isolates that carried the plasmid-located blaAmpC gene had recently visited the Indian subcontinent and we presume that they returned carrying these bacteria. Restriction fragment length polymorphism analysis using pulsed field gel electrophoresis (PFGE) suggests that at least four distinct strains existed amongst these five isolates. The two isolates that had very similar PFGE patterns had different plasmid profiles and were isolated from different locations in the hospital and at different times. This study demonstrates the ease with which highly resistant bacteria can be imported into the UK and spread within hospitals.
Cross Infection↗