bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclooxygenase-2 Selective Nonsteroidal Anti-Inflammatory Drugs and the Risk of Ischemic Stroke
Authors: Andersohn Frank , Schade René , Suissa Samy , Garbe Edeltraut
Published: May 2006

Background and Purpose—

Several randomized trials and a large number of epidemiological studies have provided evidence of an increased risk of acute myocardial infarction associated with the use of cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs). Few data are available concerning the risk of ischemic stroke associated with COX-2 inhibitors.

Methods—

We performed a nested case-control study in a cohort of 469 674 patients registered within the UK General Practice Research Database (GPRD), who had at least 1 prescription of an NSAID between June 1, 2000 and October 31, 2004. A total of 3094 cases with ischemic stroke were identified and 11 859 controls were matched on age, sex, year of cohort entry and general practice. Odds ratios (ORs) of ischemic stroke associated with the use of COX-2 selective NSAIDs were calculated by conditional logistic regression.

Results—

Current use of rofecoxib (OR=1.71; 95% CI, 1.33 to 2.18), etoricoxib (OR=2.38; 95% CI, 1.10 to 5.13), but not of celecoxib (OR=1.07; 95% CI, 0.79 to 1.44) was associated with a significantly increased risk of ischemic stroke. For rofecoxib and etoricoxib, ORs tended to increase with higher daily dose and longer duration of use and were also elevated in patients without major stroke risk factors.

Conclusions—

Our study suggests that COX-2 selective NSAIDs differ in their potential to cause ischemic cerebrovascular events. An increased risk of ischemic stroke may be influenced by additional pharmacological properties of individual COX-2 inhibitors.
Thrombolysis (Tissue Plasminogen Activator) in Stroke
Authors: Weintraub Michael I.
Published: May 2006

Background and Purpose—

Despite the success of the 1995 National Institutes of Neurological Disorders and Stroke (NINDS) study using IV recombinant tissue plasminogen activator (tPA) within 3 hours in acute stroke and its subsequent FDA approval, there has been a reluctance to use tPA because of safety and efficacy issues with high incidence of intracerebral hemorrhage, and protocol violations.

Summary of Review—

The following cases will illustrate the increased number of malpractice lawsuits generated by the controversy of “standard of care” and illustrate and educate clinicians regarding specific issues and how to avoid: (A) Failure to use tPA (loss of chance) or to transfer,
Reed versus Granbury Hospital (Texas)
: acute stroke victim taken to local hospital with tPA available only for cardiology. Wife subsequently transferred patient to nearby stroke center but no tPA given. Defendant verdict; (B) Stroke misdiagnosis (failure to diagnose, loss of chance),
Mei versus Kaiser Permanente South (San Francisco, CA)
: acute stroke while driving with ambulance taking to local hospital. Symptoms were misdiagnosed and neurologist did not see her for 6 hours. Plaintiff verdict; (C) Bleeding complications of therapy/failure of informed consent,
Harris versus Oak Valley Hospital (California
): acute stroke and hypertension treated with tPA with subsequent development of intracerebral hemorrhage. Patient alleged that tPA should not have been given. Defense verdict; (D) Expert witness testimony,
Wojcicki versus Caragher (Massachusetts
): a prominent neurologist gave “false and misleading testimony” and the Court found that the neurologist perpetrated a “fraud on the Court” intentionally and deliberately misleading the Court and jury. Court sanctioned the neurologist $88 685;
Ensink versus Mecosta County General Hospital (Michigan
): neurological testimony (plaintiff expert) regarding potential benefit of using tPA during last available 1 hour of window was felt to be “speculative”. Defendant verdict.

Conclusions—

Neurologists, emergency room physicians and hospitals are at increased liability risk if they use or do not use tPA. Detailed documentation, informed consent or timely transfer should reduce threat of legal action.
A Sufi movement in Bangladesh
Authors: Bertocci Peter J.
Published: May 2006

This article introduces the Maijbhandari Sufi brotherhood, perhaps one of the most important spiritual groupings in today's Bangladesh. Maijbhandari origins, leadership and shrines are briefly described, and the rootedness of the movement in the country's agrarian history is suggested. The roles of oral and musical performance, as well as buffalo sacrifice, as major ritual forms and practices are discussed and analysed in some depth. The article underlines the centrality of pir veneration and its associated Sufi ideation in Bangladeshi culture as well as in the country's religious politics.
Dalit rebellion against untouchability in Chakwada, Rajasthan
Authors: Bhatia Bela
Published: May 2006

This article presents a detailed case study of Dalit rebellion against untouchability in Chakwada, a village of Jaipur district in Rajasthan. The case study highlights the fact that, while many humiliating practices of the past have ceased, caste discrimination continues in many forms. Caste-based hierarchy and power are still at the heart of the traditional social order and determine, to a large extent, the kinds of lives that people live. Further, the police and the state machinery have failed to protect the constitutional rights of Dalits, and often end up aligning with forces that suppress them. In the eyes of the law-enforcing agencies, Dalits remain unequal citizens. The Chakwada story brings out the difficulties that Dalits face in breaking traditional forms of oppression. Any attempt to challenge the traditional social order makes them vulnerable to repression and violence, and also to isolation. The article also argues that this rebellion against untouchability did not really challenge the caste system itself.
The Relative Duties of a Man: Domestic Medicine in England and France, ca. 1685–1740
Authors: Smith Lisa
Published: May 2006

Although much work is currently being done on early modern women and household medicine and on early modern masculinities, historians have generally overlooked men’s roles within the home, particularly with respect to domestic medical activities. Using medical consultation letters, this article examines men’s roles as domestic caregivers and their medical decision making. During this period, manly self-management and household order were closely linked; an ideal head of household would manage himself, retain order within the household, and look after the welfare of his family.
The Experience of the Jewish Family in the Nazi Ghetto: Kovno—A Case Study
Authors: Cohen Sharon Kangisser
Published: May 2006

The intention of Hitler and his regime was the destruction of the Jewish people: their social and familial structures. Jews were separated from their families and friends as the Nazis carried out their policies of murder. The Nazi ghetto was the “last place” in which the traditional family structure was maintained. This article discusses the gradual disintegration of the family unit through the separation, deportation, and death of its members. Yet despite this physical assault on family life in the ghetto, it becomes clear that the ghetto inhabitants still maintained an “emotional” family life and built new surrogate family structures. For many, belonging to a group was an emotional as well as physical requirement for attempting to “survive” in the ghetto. Often, the family structure reversed the Nazis’ policies of degradation and attempted dehumanization of their Jewish victims. It could not, however, reverse their murders.
Black/White Interracial Marriage Trends, 1850–2000
Authors: Gullickson Aaron
Published: May 2006

This article traces the trend in black/white interracial marriage between 1850-2000, using microlevel Census samples. The results show that the frequency of interracial marriage has been highly responsive to the dynamic nature of broader race relations. The growth of the Jim Crow racial state in the South and segregation in the North led to a drastic decline in the frequency of interracial marriage from 1880 to 1930. The frequency of interracial marriage increased with the waning of this system between 1930 and 1940, but only began to increase at a steady and rapid rate in the post-civil rights era. When disaggregated by region, the results suggest a process of “latent” racism in the non-South, and one of unequal gender suppression in the South. Results by nativity and education are also discussed.
Sleep and Circadian Phase in a Ship’s Crew
Authors: Arendt Josephine , Middleton Benita , Williams Peter , Francis Gavin , Luke Claire
Published: May 2006

Numerous factors influence the increased health risks of seamen. This study investigated sleep (by actigraphy) and the adaptation of the internal clock in watch-keeping crew compared to day workers, as possible contributory factors. Fourteen watch keepers, 4 h on, 8 h off (0800-1200/2000-2400 h, 1200-1600/2400-0400 h, 1600-2000/0400-0800 h) (fixed schedule, n = 6; rotating by delay weekly, n = 8), and 12 day workers participated during a voyage from the United Kingdom to Antarctica. They kept daily sleep diaries and wore wrist monitors for continuous recording of activity. Sleep parameters were derived from activity using the manufacturer’s software and analyzed by repeated-measures ANOVA using SAS 8.2. Sequential urine samples were collected for 48 h weekly for 6-sulphatoxymelatonin measurement as an index of circadian rhythm timing. Individuals working watches of 1200-1600/2400-0400 h and 1600-2000/0400-0800 h had 2 sleeps daily, analyzed separately as main sleep (longest) and 2nd sleep. Main sleep duration was shorter in watch keepers than in day workers ( p < 0.0001). Objective sleep quality was significantly compromised in rotaters compared to both day workers and fixed watch keepers, the most striking comparisons being sleep efficiency (percentage desired sleep time spent sleeping) main sleep ( p < 0.0001) and sleep fragmentation (an index of restlessness) main sleep ( p < 0.0001). The 2nd sleep was substantially less efficient than was the main sleep ( p < 0.0001) for all watch keepers. There were few significant differences in sleep between the different watches in rotating watch keepers. Circadian timing remained constant in day workers. Timing of the 6-sulphatoxymelatonin rhythm was later for the watch of 1200-1600/2400-0400 h than for all others (1200-1600/2400-0400 h, 5.90 ± 0.85 h; 1600-2000/0400-0800 h, 1.5 ± 0.64 h; 0800-1200/ 2000-2400 h, 2.72 ± 0.76 h; days, 2.09 ± 0.68 h [decimal hours, mean ± SEM]: ANOVA, p < 0.01). This study identifies weekly changes in watch time as a cause of poor sleep in watch keepers. The most likely mechanism is the inability of the internal clock to adapt rapidly to abrupt changes in schedule.
Development of a Two-Dimension Manifold to Represent High Dimension Mathematical Models of the Intracellular Mammalian Circadian Clock
Authors: Indic Premananda , Gurdziel Katherine , Kronauer Richard E. , Klerman Elizabeth B.
Published: May 2006

A new focus for mathematical models of the circadian pacemaker involves the encapsulation within the models of detailed biological processes responsible for generating those circadian rhythms. Representing greater biological detail requires more mathematical equations, which pose a greater challenge for the analysis of such systems. Development of a method that retains the predominant dynamics while still providing biologically detailed information is advantageous. Two high-dimension mathematical models of intracellular mammalian circadian pacemakers, Leloup-Goldbeter and Forger-Peskin, with 19 and 73 differential equations, respectively, have been published. The authors projected each of these high-dimension models onto their respective manifold using proper orthogonal functions (POFs) obtained from the empirical decomposition of the model’s phase space to obtain a 2-dimension model. The resulting 2-dimension model, represented by 2 differential equations, predicts most of the salient characteristics of a biological clock including ~24-h oscillations, entrainment to an LD cycle, phase response curves, and the amplitude recovery dynamics that emerge following amplitude suppression. The manifold representation simplifies the mathematical analysis, since only 2 variables need to be observed and analyzed to understand the behavior of the biological clock. This reduced model derived from a model based on biological variables can be used for the development and analysis of mathematical models of the coupled mammalian oscillators to understand the dynamics of the integrated circadian pacemaker.
Restoration of Circadian Rhythmicity in Circadian Clock-Deficient Mice in Constant Light
Authors: Abraham Diya , Dallmann Robert , Steinlechner Stephan , Albrecht Urs , Eichele Gregor , Oster Henrik
Published: May 2006

In mammals, circadian rhythms in behavior and physiology are controlled by a central pacemaker, the SCN, and subordinated clocks throughout the body. On the molecular level, these clocks are based on transcriptional/translational feedback loops involving a set of clock genes that regulate their own transcription. Among the components driving the mammalian circadian clock are the Period 1 and 2 ( Per1 and Per2) and Cryptochrome 1 and 2 ( Cry1 and Cry2) genes. In the present study, the authors characterize the behavioral and molecular rhythms of Per2/ Cry1 double mutant mice under 3 different lighting conditions. In an LD cycle, the activity of these animals is masked by light, while in DD, the mutants lose circadian rhythmicity but exhibit strong ultradian rhythms. In LL of higher intensity, circadian rhythms are restored on the behavioral level with a drastically shortened endogenous period. Furthermore, both in the SCN and in the periphery, clock gene rhythms are restored. Based on these observations and also on the fact that light-mediated induction of Per gene expression is preserved in these mutants, the authors propose a mechanism by which endogenous ultradian rhythms may relay timed light exposure to the SCN, leading to a reinitiation of self-sustained circadian rhythms in LL.
A Comparative Study of Role Stress in Government and Private Hospital Nurses
Authors: Tankha Geetika
Published: May 2006

Stress has become the most important factor influencing individual efficacy and satisfaction in modern day occupational settings. In this context, the nursing profession is increasingly characterised by occupational stress. This study was conducted with the aim of investigating the effect of role stress in a sample of 120 nursing professionals of government and private hospitals. They were administered Organisational Role Stress Scale by Pareek (1981) in order to assess the level of stress experienced by them. The obtained results revealed that male nurses experienced significantly higher stress level as compared to females. Second, male nurses from private hospitals showed significantly higher level of stress levels than the government nurses on eight out of the ten dimensions of Organisational Role Stress Scale.
Reproductive Morbidity of Women in Karnataka
Authors: Mutharayappa R.
Published: May 2006

The main objective of the present study is to highlight the extent of reproductive health problems, the factors responsible for increasing RTI cases and to suggest appropriate strategies. Five types of obstetric problems and seven types of gynaecological problems were listed in both National Family Health Survey-2 (NFHS-2) and Reproductive and Child Health (RCH) surveys. Fewer than half the women reported at least one obstetric morbidity and more than one-tenth reported at least one gynaecological morbidity. More women in urban areas had reported obstetric morbidity whereas more women from rural areas reported gynaecological morbidity. Educated women, women who work in other activities and Scheduled Caste and Scheduled Tribe women reported that they are suffering from obstetric problems. Women who do not have toilet facilities at home and women who live in semipucca houses reported gynaecological problems. There is a relationship between age at first delivery or ‘child-birth’ and the reproductive morbidity of women. Reproductive morbidity due to abortion is high among rural women.

Data reveals that fewer than half the women who reported gynaecological problems did not seek treatment. Of the women who reported at least one symptom of gynaecological problems nearly half were in the 25–34 age group and only 50–60 per cent of them sought treatment. Education played a major role in women's health-seeking behaviour. Among those who sought treatment majority had gone to private health facilities. There is need to expand informed choices among women. Women must be empowered to take charge of their pregnancy-related needs. It is important to raise community awareness regarding early marriage and pregnancy. Misconceptions about nutrition and health care during pregnancy must be confronted at the community level and among pregnant women, and the families in which they reside.
Providing Care to Persons with Stigmatised Illnesses
Authors: Krishnatray Pradeep , Melkote Srinivas R. , Krishnatray Sangeeta
Published: May 2006

Public health challenges such as AIDS, tuberculosis, plague, and leprosy have implicitly assumed stigmatisation of patients. This article is about stigmatised illnesses, a disease where patients face medical and social challenges. Today, diseases such as leprosy, TB are curable if detected early. However, the social problem of stigma still persists. Why is it that despite the availability of treatment, persons with diseases continue to be ostracised by the community? What is the role of the health-workers? Should they be effective distributor of medicines and methods of cure or should they also empower the community to examine and reflect upon this medical cum sociological phenomenon and help the community to devise methods of providing cure as well as providing care? What are the best practices the community can follow to deal with leprosy and its social ramifications? Importantly, what are the implications for participatory communication and for effective interventions in the future? This article discusses several core themes that suggest some answers to these questions.
Patient and Staff Perspectives on Single-Sex Accommodation
Authors: Leavey Gerard , Papageorgiou Alexia , Papadopoulos Chris
Published: May 2006

The changeover to single sex accommodation in psychiatric hospitals was intended to strengthen patients' dignity, safety and privacy (DoH 2000). Previous research on patients' attitudes to single sex accommodation suggests that female patients in particular are in favour, although the views of staff are less well known. Our aim was to examine both patient and staff perspectives on single-sex accommodation. We surveyed patients in acute psychiatric wards using a patient questionnaire that covered satisfaction of care and preference for single or mixed sex accommodation. In addition we undertook brief in-depth interviews using a semi-structured questionnaire with patients and staff in order to gain a better understanding of this issue. The results revealed that safety is a major concern in determining patient satisfaction with services. Female patients were much more likely to prefer segregated accommodation than men (χ2 = 26.56, df = two, p < 0.0000). Patients suggest that diagnosis, severity of illness, and age are equally important in determining hospital accommodation and a safe, therapeutic environment. Male staff are concerned with potential allegations of sexual harassment, while women staff view single-sex accommodation as a threat to creating a more natural environment for patients. We conclude that while the majority of women patients favour single sex accommodation. The results of this study indicate that the views of patient and staff are more complex. Patient concerns of safety on psychiatric wards may not be wholly resolved by the introduction of single-sex accommodation. Clear policy guidelines and training must also be provided for staff members.
Building Learning Practices with Self-Empowered Teams for Improving Patient Safety
Authors: Singh Ranjit , Singh Ashok , Taylor John S. , Rosenthal Thomas , Singh Sonjoy , Singh Gurdev
Published: May 2006

BACKGROUND AND OBJECTIVES: Each primary care practice should be viewed as a complex adaptive micro-system with its own unique characteristics. To improve safety, under constraints of limited resources and numerous competing demands, practices need to identify those vulnerabilities that pose the greatest risks and focus efforts on these. The Objective was to develop and test a novel methodology that forms self-empowered learning teams that can prioritise safety problems based on the combination of error frequency and severity of consequences, and then devise feasible interventions.

METHODS: A survey instrument was designed and used to elicit, in qualitative terms, staff perceptions of frequency, p, and severity, s, of various types/causes of primary care errors. The qualitative responses were quantified using an algorithm that allowed for risk aversion. Relative hazard rate, h = pxs, was used as the basis for prioritising safety problems in two primary care test practices.

RESULTS: Each site identified its own set of priorities with very little overlap. Within each site there was high concordance between priorities identified by physicians, nursing and administrative staff but each site appeared to be unique. Priorities also remained stable with variation in the degree of risk aversiveness assumed in the Hazard calculation.

INTERPRETATION AND CONCLUSIONS: The method aided formation of central ‘attractors’ in the form of self-empowered effective learning teams with a common vision to help their complex micro-systems to adapt and thrive. This pro-active type of methodology helps in creating a sustainable safety culture, and has been adapted for other health-care settings and physician training.
Teaching and Assessing in Clinical Practice
Authors: Kassean H.K. , Rajaram R.
Published: May 2006

A structured teaching programme was designed for second year student nurses who were on a 1-week placement at the ENT hospital of Mauritius. As part of the programme, this article discusses how a teaching session on tracheostomy suctioning and humidification was implemented. The teaching session incorporated both the pedagogical and andragogical techniques in order to make the learning experience meaningful for the students. The learning outcomes were evaluated in terms of, knowledge, skill and attitude and were found to have been mostly met. However, more practice was required on the part of the students in order to become more proficient. Formal training and assessing in clinical practice can contribute significantly towards improving the quality of care and satisfying the needs of patients.
E-health Governance Model and Strategy in India
Authors: Khandelwal Atal
Published: May 2006

The article presents a framework for e-health governance complete solutions through a relational model that emphasise e-health strategies to develop and implement. It simplifies the task of developing, deploying, and managing complex, integrated, and standards-compliant e-health governance solutions. It also provides commonly used health services such as access to citizen and health records, access control and authentication services, public key infrastructure, and support for digital systems.
Computer-Assisted Physician Requirement Planning
Authors: Ghosh Basu , George Cruz
Published: May 2006

Hospital administrations in the developing–world face great challenges to meet the demand for more physicians in hospitals. A computer-based physician requirement planning model is a user-friendly approach in response to such demands. This article presents a new method-ology based on a Graphic User Interface (GUI) using Java. Information on work days/hours, activity-wise standard times and annual workload information, bed capacity and occupancy figures are inputted in a visual display screen and the model generates activity-wise and overall physician requirements. Current availability is entered and prevailing productivity levels are estimated. An institutional summary presents overall and specialty-wise current availability and requirement of physicians. Computerisation empowers policy makers/planners to respond promptly to requests by hospitals for manpower assessment and decide objectively on additional posts. It enables health administration to visualize human resource implications of changing utilisation scenarios and variation in model parameters.
The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera
Authors: Lippert Eric , Boissinot Marjorie , Kralovics Robert , Girodon François , Dobo Irène , Praloran Vincent , Boiret-Dupré Nathalie , Skoda Radek C. , Hermouet Sylvie
Published: May 2006

We determined the allelic frequency of the JAK2-V617F mutation in DNA and assessed the expression levels of the mutant and wild-type JAK2 mRNA in granulocytes from 60 patients with essential thrombocythemia (ET) and 62 patients with polycythemia vera (PV) at the time of diagnosis. Using allele-specific quantitative polymerase chain reaction (qPCR), we detected JAK2-V617F in 75% of ET and 97% of PV at diagnosis. The total JAK2 mRNA levels were elevated in ET, PV, and secondary and idiopathic erythrocytosis, suggesting that hyperactive hematopoiesis alters JAK2 expression. The expression levels of JAK2-V617F mRNA were variable but strongly correlated with the allelic ratio of JAK2-V617F determined in DNA. Thus, differences in JAK2-V617F expression, markedly lower in ET than in PV, reflected different percentages of granulocytes carrying the mutation. Moreover, allelic ratios higher than 50% JAK2-V617F, indicating the presence of granulocytes homozygous for JAK2-V617F, were found in 70% of PV at diagnosis but never in ET.
Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma: an analysis of patients receiving conventional-dose chemotherapy in Medical Research Council UK multiple myeloma trials
Authors: Drayson Mark , Begum Gulnaz , Basu Supratik , Makkuni Sudhaker , Dunn Janet , Barth Nicola , Child J. Anthony
Published: May 2006

While investigating 2592 patients enrolled in multicenter myeloma trials, we found light chain–only (LCO) patients had worse median survival times (1.9 years) than patients with IgA and IgG paraproteins (2.3 and 2.5 years, respectively) (P < .001). However, IgA and IgG patients with levels of LC excretion similar to those of LCO patients also had poor survival times because of renal failure, resulting in worse survival during induction therapy and at relapse with no difference in progression-free survival between LCO and IgG patients. LC excretion was higher for λ than for κ types, but there was no difference in survival between the 2 LC types when stratified for level of LC excretion, indicating that care of renal function is vital to improving the survival of any patient with LC excretion. LCO patients were younger (P = .001), had worse performance status (P = .001), and had more lytic lesions (P < .001), perhaps reflecting late and missed diagnoses in younger and older LCO patients, respectively. No differences were observed between IgA and IgG patients in presentation characteristics, response, or survival from disease progression. The worse survival of IgA patients was attributed to shorter progression-free survival (median, 1.2 vs 1.6 years; P < .001), which is important for maintenance therapy.
Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation
Authors: Yang Xuwei , Lee Koutetsu , Said Jonathan , Gong Xun , Zhang Ke
Published: May 2006

Chromosomal translocations (CTs) between immunoglobulin (Ig) genes and the BCL6 proto-oncogene are frequently associated with diffuse large B-cell lymphomas (DLBCLs) and follicular lymphomas (FLs) and are implicated in the development of these lymphomas. However, whether Ig/BCL6 translocation per se is sufficient to drive malignant transformation is not clear. To understand the biology of Ig/BCL6-translocated cells prior to their malignant transformation, we developed a system capable of detecting 1 to 3 Igμ/BCL6 CT cells in 1 million mixed cells through the detection of chimeric Iμ-BCL6E2 and BCL6E1-Cμ1 transcripts that reflect reciprocal Igμ/BCL6 translocations. The chimeric transcripts that existed in the vast majority of normal lymphoid tissues are due to Igμ/BCL6 CT and were not generated from trans-splicing. Both Iμ-BCL6E2 and BCL6E1-Cμ1 transcripts were coexpressed in the same cell populations. The Ig/BCL6 recombination junctions themselves were isolated from B-cell subpopulations expressing the Iμ-BCL6 transcripts. The appearance of Igμ/BCL6 CT was associated with cells expressing germinal center but not naive B-cell markers. This study shows that Ig/BCL6 translocations occur in germinal center–stage B cells in healthy humans, and that Ig/BCL6 CTs per se are not likely sufficient to cause the malignant transformation in the context of human B cells.
Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART
Authors: Epple Hans-Jörg , Loddenkemper Christoph , Kunkel Desirée , Tröger Hanno , Maul Jochen , Moos Verena , Berg Erika , Ullrich Reiner , Schulzke Jörg-Dieter , Stein Harald , Duchmann Rainer , Zeitz Martin , Schneider Thomas
Published: May 2006

Recent evidence indicates that regulatory T cells (Tregs) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal Tregs in HIV infection are available. In this study, we compared the frequency of Tregs in duodenal mucosa and peripheral blood (PB) of 13 treatment-naive and 13 suppressively treated HIV-infected patients with that of 6 patients with norovirus infection and 12 healthy controls. Tregs were quantified by immunohistochemistry (CD3/FOXP3) and further characterized (CD25, CTLA-4, GITR) by immunohistochemistry, immunofluorescence, and fluorescence-activated cell sorting (FACS). Both the frequency and the absolute count of mucosal Tregs were highly increased in untreated HIV patients but were normal in treated HIV patients. In contrast, in peripheral blood of HIV patients, the absolute number of Tregs was not increased, and their frequency was only slightly elevated. In norovirus infection, frequency of mucosal Tregs in the CD4+ T-cell subset was not elevated. The high increase in count and frequency of mucosal Tregs seems to be a characteristic feature of untreated HIV infection, suggesting a significant contribution of Tregs to the pathogenesis of HIV disease. Their role may be 2-edged: attenuating HIV-induced immune hyperactivation while suppressing the immune response to HIV and mucosal pathogens.
Genomic patterns of pathogen evolution revealed by comparison of Burkholderia pseudomallei, the causative agent of melioidosis, to avirulent Burkholderia thailandensis
Authors: Yu Yiting , Kim H Stanley , Chua Hui Hoon , Lin Chi Ho , Sim Siew Hoon , Lin Daoxun , Derr Alan , Engels Reinhard , DeShazer David , Birren Bruce , Nierman William C , Tan Patrick
Published: May 2006

Background

The Gram-negative bacterium Burkholderia pseudomallei (Bp) is the causative agent of the human disease melioidosis. To understand the evolutionary mechanisms contributing to Bp virulence, we performed a comparative genomic analysis of Bp K96243 and B. thailandensis (Bt) E264, a closely related but avirulent relative.

Results

We found the Bp and Bt genomes to be broadly similar, comprising two highly syntenic chromosomes with comparable numbers of coding regions (CDs), protein family distributions, and horizontally acquired genomic islands, which we experimentally validated to be differentially present in multiple Bt isolates. By examining species-specific genomic regions, we derived molecular explanations for previously-known metabolic differences, discovered potentially new ones, and found that the acquisition of a capsular polysaccharide gene cluster in Bp, a key virulence component, is likely to have occurred non-randomly via replacement of an ancestral polysaccharide cluster. Virulence related genes, in particular members of the Type III secretion needle complex, were collectively more divergent between Bp and Bt compared to the rest of the genome, possibly contributing towards the ability of Bp to infect mammalian hosts. An analysis of pseudogenes between the two species revealed that protein inactivation events were significantly biased towards membrane-associated proteins in Bt and transcription factors in Bp.

Conclusion

Our results suggest that a limited number of horizontal-acquisition events, coupled with the fine-scale functional modulation of existing proteins, are likely to be the major drivers underlying Bp virulence. The extensive genomic similarity between Bp and Bt suggests that, in some cases, Bt could be used as a possible model system for studying certain aspects of Bp behavior.
Recall of intestinal helminthiasis by HIV-infected South Africans and avoidance of possible misinterpretation of egg excretion in worm/HIV co-infection analyses
Authors: Adams Vera J , Markus Miles B , Kwitshana Zilungile L , Dhansay Muhammad A , van der Merwe Lize , Walzl Gerhard , Fincham John E
Published: May 2006

Background

Ascariasis and HIV/AIDS are often co-endemic under conditions of poverty in South Africa; and discordant immune responses to the respective infections could theoretically be affecting the epidemic of HIV/AIDS in various ways. It is well-known that sensitisation to helminthic antigens can aggravate or ameliorate several non-helminthic diseases and impair immunisation against cholera, tetanus and tuberculosis. The human genotype can influence immune responses to Ascaris strongly. With these factors in mind, we have started to document the extent of long-term exposure to Ascaris and other helminths in a community where HIV/AIDS is highly prevalent. In more advanced studies, objectives are to analyse relevant immunological variables (e.g. cytokine activity and immunoglobulin levels). We postulate that when Ascaris is hyperendemic, analysis of possible consequences of co-infection by HIV cannot be based primarily on excretion vs non-excretion of eggs.

Methods

Recall of worms seen in faeces was documented in relation to the age of adult volunteers who were either seropositive (n = 170) or seronegative (n = 65) for HIV. Reasons for HIV testing, deworming treatments used or not used, date and place of birth, and duration of residence in Cape Town, were recorded. Confidence intervals were calculated both for group percentages and the inter-group differences, and were used to make statistical comparisons.

Results

In both groups, more than 70% of participants were aware of having passed worms, often both when a child and as an adult. Most of the descriptions fitted Ascaris. Evidence for significantly prolonged exposure to helminthic infection in HIV-positives was supported by more recall of deworming treatment in this group (p < 0.05). Over 90% of the participants had moved to the city from rural areas.

Conclusion

There was a long-term history of ascariasis (and probably other helminthic infections) in both of the groups that were studied. In women in the same community, and in children living where housing and sanitation are better, Ascaris sero-prevalence exceeded egg-prevalence by two- and three-fold, respectively. For ongoing and future analyses of possible consequences of co-infection by Ascaris (and/or other helminths) and HIV/AIDS (and/or other bystander conditions), comparisons must be based mainly on disease-related immunological variables. Especially in adults, comparisons cannot be based only on the presence or absence of eggs in excreta.
Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation
Authors: Zhang Zhuangyu , Machac Josef , Helft Gerard , Worthley Stephen G , Tang Cheuk , Zaman Azfar G , Rodriguez Oswaldo J , Buchsbaum Monte S , Fuster Valentin , Badimon Juan J
Published: May 2006

Background

Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of 18F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model.

Methods

Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta.

Results

Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity.

Conclusion

PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.
Fluorophotometry as a diagnostic tool for the evaluation of dry eye disease
Authors: Fahim Magid M , Haji Shamim , Koonapareddy Chakravarthy V , Fan Vincent C , Asbell Penny A
Published: May 2006

Background

Dry eye disease is a common debilitating ocular disease. Current diagnostic tests used in dry eye disease are often neither sensitive nor reproducible, making it difficult to accurately diagnose and determine end points for clinical trials, or evaluate the usefulness of different medications in the treatment of dry eye disease. The recently developed fluorophotometer can objectively detect changes in the corneal epithelium by quantitatively measuring its barrier function or permeability. The purpose of the study is to investigate the use of corneal fluorescein penetration measured by the fluorophotometer as a diagnostic tool in the evaluation of dry eye patients.

Methods

Dry eye patients (16 eyes), who presented with a chief complaint of ocular irritation corresponding with dry eye, low Schirmer's one test (<10 mm after 5 minutes) and corneal fluorescein staining score of more than two, were included in the study. Normal subjects (16 eyes), who came for refraction error evaluation, served as controls. Institutional Review Board (IRB) approved consent was obtained before enrolling the subjects in the study and all questions were answered while explaining the risks, benefits and alternatives. All Fluorophotometry of the central corneal epithelium was done utilizing the Fluorotron Master (TradeMark). Each eye had a baseline fluorescein scan performed, after which 50 l of 1% sodium fluorescein dye was instilled. Three minutes later, the fluorescein was washed with 50 ml of normal saline. Fluorescein scans were then started immediately after washing and were recorded at 10, 20, 40, and 60 minutes thereafter. The corneal peak values of fluorescein concentration were recorded within the central cornea in both dry eyes and in controls.

Results

Ten minutes after fluorescein installition, patients with dry eye disease averaged a five-fold increase in corneal tissue fluorescein concentration (mean = 375.26 ± 202.67 ng/ml) compared with that of normal subjects (mean = 128.19 ± 85.84 ng/ml). Sixty minutes after dye installation, patients with dry eye disease still revealed higher corneal tissue fluorescein concentration (mean = 112.87 ± 52.83 ng/ml) compared with that of controls (mean = 40.64 ± 7.96 ng/ml), averaging a three-fold increase.

Conclusion

Patients with dry eye disease demonstrated an increased corneal permeability and a slower rate of elimination to topically administered fluorescein when measured by the fluorophotometer. This suggests that fluorophotometry may serve as a valuable quantitative and objective tool for the diagnosis of dry eye disease, and in following patients' response to new treatment modalities. Fluorophotometry may serve as an objective non-invasive tool for end-point analysis in clinical trials of new treatments for dry eye disease.
The air quality impacts of road closures associated with the 2004 Democratic National Convention in Boston
Authors: Levy Jonathan I , Baxter Lisa K , Clougherty Jane
Published: May 2006

Background

The Democratic National Convention (DNC) in Boston, Massachusetts in 2004 provided an opportunity to evaluate the impacts of a localized and short-term but potentially significant change in traffic patterns on air quality, and to determine the optimal monitoring approach to address events of this nature. It was anticipated that the road closures associated with the DNC would both influence the overall air pollution level and the distribution of concentrations across the city, through shifts in traffic patterns.

Methods

To capture these effects, we placed passive nitrogen dioxide badges at 40 sites around metropolitan Boston before, during, and after the DNC, with the goal of capturing the array of hypothesized impacts. In addition, we continuously measured elemental carbon at three sites, and gathered continuous air pollution data from US EPA fixed-site monitors and traffic count data from the Massachusetts Highway Department.

Results

There were significant reductions in traffic volume on the highway with closures north of Boston, with relatively little change along other highways, indicating a more isolated traffic reduction rather than an across-the-board decrease. For our nitrogen dioxide samples, while there was a relatively small change in mean concentrations, there was significant heterogeneity across sites, which corresponded with our a priori classifications of road segments. The median ratio of nitrogen dioxide concentrations during the DNC relative to non-DNC sampling periods was 0.58 at sites with hypothesized traffic reductions, versus 0.88 for sites with no changes hypothesized and 1.15 for sites with hypothesized traffic increases. Continuous monitors measured slightly lower concentrations of elemental carbon and nitrogen dioxide during road closure periods at monitors proximate to closed highway segments, but not for PM2.5 or further from major highways.

Conclusion

We conclude that there was a small but measurable influence of DNC-related road closures on air quality patterns in the Boston area, and that a low-cost monitoring study combining passive badges for spatial heterogeneity and continuous monitors for temporal heterogeneity can provide useful insight for community air quality assessments.
Exposure assessment in investigations of waterborne illness: a quantitative estimate of measurement error
Authors: Jones Andria Q , Dewey Catherine E , Doré Kathryn , Majowicz Shannon E , McEwen Scott A , Waltner-Toews David
Published: May 2006

Background

Exposure assessment is typically the greatest weakness of epidemiologic studies of disinfection by-products (DBPs) in drinking water, which largely stems from the difficulty in obtaining accurate data on individual-level water consumption patterns and activity. Thus, surrogate measures for such waterborne exposures are commonly used. Little attention however, has been directed towards formal validation of these measures.

Methods

We conducted a study in the City of Hamilton, Ontario (Canada) in 2001–2002, to assess the accuracy of two surrogate measures of home water source: (a) urban/rural status as assigned using residential postal codes, and (b) mapping of residential postal codes to municipal water systems within a Geographic Information System (GIS). We then assessed the accuracy of a commonly-used surrogate measure of an individual's actual drinking water source, namely, their home water source.

Results

The surrogates for home water source provided good classification of residents served by municipal water systems (approximately 98% predictive value), but did not perform well in classifying those served by private water systems (average: 63.5% predictive value). More importantly, we found that home water source was a poor surrogate measure of the individuals' actual drinking water source(s), being associated with high misclassification errors.

Conclusion

This study demonstrated substantial misclassification errors associated with a surrogate measure commonly used in studies of drinking water disinfection byproducts. Further, the limited accuracy of two surrogate measures of an individual's home water source heeds caution in their use in exposure classification methodology. While these surrogates are inexpensive and convenient, they should not be substituted for direct collection of accurate data pertaining to the subjects' waterborne disease exposure. In instances where such surrogates must be used, estimation of the misclassification and its subsequent effects are recommended for the interpretation and communication of results. Our results also lend support for further investigation into the quantification of the exposure misclassification associated with these surrogate measures, which would provide useful estimates for consideration in interpretation of waterborne disease studies.
Causal criteria and counterfactuals; nothing more (or less) than scientific common sense
Authors: Phillips Carl V , Goodman Karen J
Published: May 2006

Two persistent myths in epidemiology are that we can use a list of "causal criteria" to provide an algorithmic approach to inferring causation and that a modern "counterfactual model" can assist in the same endeavor. We argue that these are neither criteria nor a model, but that lists of causal considerations and formalizations of the counterfactual definition of causation are nevertheless useful tools for promoting scientific thinking. They set us on the path to the common sense of scientific inquiry, including testing hypotheses (really putting them to a test, not just calculating simplistic statistics), responding to the Duhem-Quine problem, and avoiding many common errors. Austin Bradford Hill's famous considerations are thus both over-interpreted by those who would use them as criteria and under-appreciated by those who dismiss them as flawed. Similarly, formalizations of counterfactuals are under-appreciated as lessons in basic scientific thinking. The need for lessons in scientific common sense is great in epidemiology, which is taught largely as an engineering discipline and practiced largely as technical tasks, making attention to core principles of scientific inquiry woefully rare.