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Biomedical subjects

J Murray

Publications and source records attributed to J Murray.

At least 127 records · Page 7Linked to original sources

Human immunodeficiency virus and the outcome of treatment for new and recurrent pulmonary tuberculosis in African patients.

The purpose of this study was to evaluate the impact of human immunodeficiency virus (HIV) infection on treatment for tuberculosis (TB). The study population comprised 28,522 black Southern African gold miners. Patients with sputum culture-positive new or recurrent pulmonary TB diagnosed in 1995 were prospectively enrolled in the cohort. Directly observed therapy (DOT) was practiced and outcomes were assessed at 6 mo after treatment was begun. There were 376 cases of TB (incidence 1,318 per 100,000), of which 190 (50%) were HIV positive and 82 (22%) had recurrent TB. There was no association between HIV status and history of previous TB or drug resistance. Neither the treatment interruption rate (2%) nor the rate at which patients transferred out of the treatment program (1.6%) were associated with HIV status. Excluding deaths, cure rates were similar for HIV-positive and HIV-negative patients (89% versus 88%), but significantly lower in those with recurrent than in those with new TB (77% versus 92%). Mortality was 0.5% in HIV-negative patients versus 13.7% in HIV-positive patients, and in the latter group was associated with CD4(+) lymphocyte depletion. Autopsy examination showed that in HIV-positive patients, early mortality was due to TB whereas late deaths were most commonly due to cryptococcal pneumonia. The study showed that a well-run TB control program can result in acceptable cure rates even in a population with a very high incidence of TB and HIV infection. Particular vigilance is needed for concurrent infections, which may contribute significantly to mortality during treatment of TB in HIV-positive patients.

AIDS-Related Opportunistic Infections↗

Use of miniradiographs to detect silicosis. Comparison of radiological with autopsy findings.

Radiological and routine autopsy findings from 241 South African gold miners were compared, using pathology as the "gold standard." Previous annual screening miniradiographs were read independently by two readers, using the International Labor Office (ILO) grading system, without reference to personal identifiers. Individual and consensus silicosis grades were recorded for each subject. When pathological and radiological silicosis were defined as any abnormal grade, the sensitivity and specificity of the radiological diagnosis was 67.5% and 80%, with positive and negative predictive values of 63% and 83%. Most undetected autopsy silicosis was early-grade. Using higher pathological and radiological grades to define silicosis (5 nodules or more and ILO grades 1/1 and above), sensitivity and specificity increased to 71% and 96%, and positive and negative predictive values increased to 76% and 95%, respectively. Use of a consensus grade made little difference to results from individual readers. For each radiological definition, sensitivity was considerably higher than, but specificity was similar to, that found in a previous study of South African gold miners which used the same pathology source and standard sized films. The difference between these two study findings, and unexpected demonstration of higher sensitivity from miniradiographs, suggests that further research is required into factors affecting radiological interpretation before silicosis grading can be considered to be adequately standardized.

Adult↗

Imprecision in medical communication: study of a doctor talking to patients with serious illness.

Uncertainty is believed to be a central feature in illness experiences. Conversations between a consultant hematologist and 61 seriously ill patients were transcribed, entered on a database and scrutinized for patterns of language uncertainty by linguistic concordancing analysis. Transcripts were then discussed in detail with the hematologist, and techniques of protocol analysis were used to gain insight into his thought processes during consultations. The main findings were that the doctor used many more expressions of uncertainty than did patients: that evaluative terms were widely used to reassure rather than to worry patients; and that patients and doctor together used certain key terms ambiguously, in a manner which allowed the doctor to feel that facts were not misrepresented while perhaps permitting the patient to feel reassured.

Hematologic Diseases↗

Microbiological status of Australian sheep meat.

Two studies were undertaken to determine the microbiological status of sheep carcass meat and frozen, bulk-packed sheep meat produced in Australia. Samples were collected from 470 sheep carcasses and 415 cartons of frozen sheep trimmings over a period of approximately 12 months. Samples were collected from plants processing sheep carcasses for domestic or export markets. On carcasses, where bacterial counts were obtained, the mean of the log10 aerobic plate count (APC) was 3.92/cm2, the geometric mean of the most probable number (MPN) per square centimeter of Escherichia coli (biotype I) was 23, and the geometric mean of the coliform count was 38 MPN per cm2. A high percentage (75%) of samples was positive for E. coli (biotype I), 81% were positive for coliforms, 5.74% were positive for Salmonella spp., and 1.29% were positive for Campylobacter. Bacterial counts were higher on carcasses chilled over a weekend than on carcasses chilled for 24 h. The total number of bacteria on carcasses processed for domestic markets was similar to that on carcasses processed for export markets. E. coli O157 was not isolated from any of the 465 samples tested. Of the frozen export samples that tested positive, the mean of the log10 APC was 3.47/g, the geometric mean of the E. coli (biotype I) count was 9 MPN per g, and the geometric mean of the coliform count was 19 MPN per g. Of the frozen export samples tested, 48% were positive for E. coli (biotype I), 58% were positive for coliforms, and 6.5% were positive for Salmonella spp. E. coli O157 was recovered from 1 of 343 frozen sheep meat samples tested (0.29%). Bacterial counts were higher on samples of domestic product than on samples of export product. Results from both surveys are compared with data from similar studies conducted in other countries.

Abattoirs↗

Comparative sequence analysis of human minisatellites showing meiotic repeat instability.

The highly variable human minisatellites MS32 (D1S8), MS31A (D7S21), and CEB1 (D2S90) all show recombination-based repeat instability restricted to the germline. Mutation usually results in polar interallelic conversion or occasionally in crossovers, which, at MS32 at least, extend into DNA flanking the repeat array, defining a localized recombination hotspot and suggesting that cis-acting elements in flanking DNA can influence repeat instability. Therefore, comparative sequence analysis was performed to search for common flanking elements associated with these unstable loci. All three minisatellites are located in GC-rich DNA abundant in dispersed and tandem repetitive elements. There were no significant sequence similarities between different loci upstream of the unstable end of the repeat array. Only one of the three loci showed clear evidence for putative coding sequences near the minisatellite. No consistent patterns of thermal stability or DNA secondary structure were shared by DNA flanking these loci. This work extends previous data on the genomic environment of minisatellites. In addition, this work suggests that recombinational activity is not controlled by primary or secondary characteristics of the DNA sequence flanking the repeat array and is not obviously associated with gene promoters as seen in yeast.

CpG Islands↗

Economic climate and cultural diversity: a merging picture.

This article explores the merging of a single nonprofit hospital with a nonprofit health care system of hospitals. It also provides the unique financial history of health care reimbursement in California that makes such merges imperative for the success of single hospitals. A unique patient-focused care model, shared governance, and the implications in the financial diversity of merging health care entities also are discussed.

California↗

Pneumocystis carinii pneumonia in HIV infected patients from South Africa.

OBJECTIVE: To compare the spectrum of pulmonary disease in human immunodeficiency virus positive patients of African and European origin, with particular reference to Pneumocystis carinii pneumonia. DESIGN: Descriptive study with retrospective record review. SETTING: Tertiary care, university teaching hospitals in Johannesburg, South Africa. SUBJECTS: Sixty seven HIV-infected patients and 36 HIV-negative renal transplant patients (who served as controls) whose sputa were negative for tuberculosis and Pneumocystis carinii, and who had fibreoptic bronchoscopic evaluation for pulmonary disease between January 1985 and August 1992. MEASUREMENTS: Histological and cytological evaluation of pulmonary diseases. RESULTS: In the HIV infected group Pneumocystis carinii pneumonia was the most frequent disease in patients of both African and European origin but occurred less commonly in Africans than in Europeans (27.3% and 58.8%, respectively; p = 0.01). There was no statistically significant difference between patients of African and European origin in the frequency of any other diagnosis. In the renal transplant group the most frequent diagnosis was non-specific interstitial pneumonitis (Africans 33.3%, Europeans 37.0%), followed by Pneumocystis carinii pneumonia (Africans 22.2%, European 14.8%). There was no difference between HIV-infected and renal transplant patients in the frequency of any diagnosis. CONCLUSION: Pneumocystis carinii pneumonia should be considered in the diagnosis of HIV-infected African patients with pulmonary disease whose sputum smears for tuberculosis are negative.

AIDS-Related Opportunistic Infections↗

EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer's disease: I--Factors associated with carer burden.

BACKGROUND: The challenges presented by the increasing public health and social impact of caring for people with dementia have become clear in recent years. Previous research has identified that, while there are positive as well as negative elements to the caring role, carers are at high risk of mental health problems and that the comprehensive burden of caring has social, economic and health based elements. Co-resident carers, especially spouses, are of primary importance in maintaining people with dementia in their own homes in the community rather than in institutional settings which may be both more costly and have greater environmental poverty. There have, however, been few studies which have sought to investigate factors associated with carer burden and differences and similarities between countries. In this study we aimed to produce a cross-national profile of co-resident spouse carers across the European Community, with particular attention to: living arrangements; formal and informal support; service satisfaction; perceived burden; and psychological well-being. METHOD: Twenty co-resident spouse carers of people with NINCDS-ADRDA probable dementia, who had been diagnosed as such within the past 12-36 months, were recruited from service contacts in each of 14 out of the 15 countries of the EU. All completed a semi-structured interview which included: sociodemographic data; data on health and social service use; the Carer Burden Inventory (CBI); the General Health Questionnaire-12 (GHQ-12); and open-ended qualitative questions about the experience of caring. RESULTS: Two hundred and eighty couples were recruited. There was marked variation in all variables of interest between countries, but there were consistently high ratings of carer burden (mean CBI scores between 28 and 52) and psychological distress (between 40% and 75% scoring 4 or more on the GHQ-12). Using multivariate analyses (generalized linear modelling) to estimate the individual associations of variables of interest with carer burden, controlling for the effects of all other variables in the model, the following results were obtained: 11.4% (p = 0.003) of the variance was accounted for by between-country variation; 4.9% (p < 0.001) by expressed financial dissatisfaction; 4.5% (p = 0.001) by lower carer age; 3.2% (p = 0.004) by difficulties with spouse behavioural deficits; and 2.0% (p = 0.024) by perceived negative social reactions. There was a low level of contact with support groups and Alzheimer's disease societies despite the samples having been of service contacts. CONCLUSIONS: This study confirms the high level of burden and mental distress in spouse carers for people with Alzheimer's disease in the European Community. It suggests that there are elements of burden which may vary by country but also elements which have a common effect in all. These data suggest avenues for the primary and secondary prevention of burden by addressing clinical issues (e.g. behavioural disturbance); public attitudes and education (e.g. negative social reactions); economic support for carers (e.g. financial dissatisfaction); and higher risk groups (e.g. younger spouse carers).

Aged↗

Role of neutrophil apoptosis in the resolution of pulmonary inflammation.

Neutrophil-mediated lung injury may result from one or more of the following possible causes: 1) loss of the normal mechanisms that regulate and switch off neutrophil influx, 2) inappropriate or uncontrolled neutrophil activation within the lung, 3) inhibition of neutrophil apoptosis, and 4) impairment or saturation of the normal macrophage-dependent process for the removal of apoptotic neutrophils. Current in vitro data indicate that many factors operating at the inflamed site (e.g. cytokines, growth factors, chemotactic peptides, hypoxia, acidosis, etc.) serve a dual function in both priming and activating these cells, and delay apoptosis. The observation that the rate of eosinophil apoptosis can be accelerated by corticosteroid therapy in vivo suggests a novel mode of action for this drug and indicates that targeting this process in other granulocyte-dependent inflammatory conditions may offer a novel therapeutic approach in inflammatory lung disease.

Animals↗

Statistical issues for HIV surrogate endpoints: point/counterpoint. An NIAID workshop.

This paper summarizes the proceedings of an NIAID-sponsored workshop on statistical issues for HIV surrogate endpoints. The workshop brought together statisticians and clinicians in an attempt to shed light on some unresolved issues in the use of HIV laboratory markers (such as HIV RNA and CD4+ cell counts) in the design and analysis of clinical studies and in patient management. Utilizing a debate format, the workshop explored a series of specific questions dealing with the relationship between markers and clinical endpoints, and the choice of endpoints and methods of analysis in clinical studies. This paper provides the position statements from the two debaters on each issue. Consensus conclusions, based on the presentations and discussion, are outlined. While not providing final answers, we hope that these discussions have helped clarify a number of issues, and will stimulate further consideration of some of the highlighted problems. These issues will be critical in the proper assessment and use of future therapies for HIV disease.

Biomarkers↗

Routine helical computed tomographic evaluation of the mediastinum in high-risk blunt trauma patients.

BACKGROUND: The indications and method of evaluation of the mediastinum in blunt deceleration trauma are controversial and vary among centers. Most centers practice a policy of angiographic evaluation only in the presence of an abnormal mediastinum on chest radiography. Routine aortography in the absence of any mediastinal abnormality is not widely practiced. Helical computed tomographic (CT) scan has been successfully used in recent studies in the evaluation of the thoracic aorta. OBJECTIVE: To determine the role of routine helical CT scan evaluation of the mediastinum in patients involved in high-speed deceleration injuries, irrespective of chest radiographic findings. DESIGN: A prospective study over a 1-year period. Included in the study were patients with high-speed deceleration injuries who required CT evaluation of the head or abdomen. This group of patients underwent routine helical CT evaluation of the mediastinum irrespective of chest radiographic findings. SETTING: Large, urban, academic level I trauma center. RESULTS: A total of 112 trauma patients fulfilled the criteria for study inclusion. Overall, there were 9 patients (8.0%) with aortic rupture. Four (44.4%) of these patients had a normal mediastinum on the initial chest x-ray film and the diagnosis was made by CT scan. The CT scan was diagnostic in 8 of the aortic ruptures (intimal tear or pseudoaneurysm) and was suggestive of aortic injury but not diagnostic in 1 patient with brachiocephalic artery injury. In 42 patients (37.5%), there was a widened mediastinum: an aortic rupture was diagnosed in 5 of them (11.9%) and a spinal fracture in 9 (21.4%). One patient had both aortic rupture and spinal injury. CONCLUSIONS: The incidence of aortic injury in patients with high-speed deceleration injury is high. A significant proportion of patients with aortic injury have a normal mediastinum on the initial chest radiograph. There is a high incidence of spinal injuries in the presence of a widened mediastinum. We recommend that all trauma patients with high-risk deceleration injuries undergo routine helical CT evaluation of the mediastinum irrespective of chest radiographic findings.

Accidental Falls↗

Identification of an immunodominant sequential epitope in glycoprotein G of herpes simplex virus type 2 that is useful for serotype-specific diagnosis.

A series of 67 oligopeptides that spanned the open reading frame of herpes simplex virus type 2 (HSV-2) glycoprotein G (gG2) were synthesized and tested for reactivity with 173 serum specimens collected from 117 individuals. The oligopeptides were made as multiple antigenic peptides consisting of four copies of a unique sequence attached to a branched lysine core and separated from the core by four glycine residues. The sera included HSV antibody-negative samples as well as sera from individuals from whom HSV had been isolated. Isolated viruses were typed by indirect fluorescence using a panel of type-specific monoclonal antibodies. One peptide, corresponding to residues 561 to 578 of gG2, did not react with any sera lacking HSV-specific antibodies of with sera from HSV-1-infected individuals, but did react with sera from HSV-2-infected individuals. For sera taken seven or more days after initialclinical lesions, the detection rate of the peptide was 92% (47/51), comparable with the 98% (50/51) of truncated glycoprotein D, a sensitive type-common reagent. We conclude that this peptide, of structure (PEEFEGAGDGEPPEDDDSG4)K3A, is an immunodominant type-specific epitope for human antibodies and should be useful for type-specific serodiagnosis of HSV-2. Surprisingly, the epitope lies within one of the most conserved regions of gG1 and gG2. The test can distinguish an initial HSV-2 infection in the presence of a preexisting HSV-1 infection.

Enzyme-Linked Immunosorbent Assay↗

Antioxidant defenses influence HIV-1 replication and associated cytopathic effects.

HIV-infected cells often exhibit reduced levels of antioxidant enzymes and thiols. To investigate the role of cellular antioxidant defenses in the progression of an acutely spreading HIV-1 infection, human Sup-T1 T cells were engineered to overexpress the selenium-dependent glutathione peroxidase, GSHPx-1. This enzyme represents a major cellular defense mechanism against toxicity associated with reactive oxygen species (ROS). T cells engineered to produce elevated GSHPx-1 activity displayed accelerated viral replication and associated cytopathic effects compared to control cells. Conversely, the inhibition of the synthesis of glutathione with buthione sulfoximine (BSO) resulted in the attenuation of viral replication in Sup-T1 cells. Similarly, exposure of human peripheral blood lymphocytes (PBLs) to low, nontoxic levels of BSO resulted in an approximately 80% decline in HIV-1 replication as indicated by Western blot analysis of viral proteins.

Animals↗

Penetrating cardiac injuries: a prospective study of variables predicting outcomes.

BACKGROUND: Penetrating cardiac injuries are one of the leading causes of death from urban violence. STUDY DESIGN: This is a prospective, 1-year study in a Level I Trauma Center with the objective of analyzing: (1) the parameters measuring the physiologic condition of patients sustaining penetrating cardiac injuries in the field during transport and on arrival, (2) the cardiovascular-respiratory score (CVRS) component of the trauma score, (3) the mechanism and anatomic site of injury, (4) the presence or absence of tamponade, and (5) the cardiac rhythm as a predictor of outcomes. We attempted to correlate cardiac injury grade (AAST-OIS) with mortality. Our main intervention was thoracotomy for resuscitation and definitive repair of cardiac injury. Main outcomes measures were all parameters measuring the physiologic condition of patients, CVRS, mechanism and anatomic site of injury, operative findings and maneuvers, mortality, and grade of injury. RESULTS: The study consisted of 60 patients sustaining penetrating cardiac injuries, 35 gunshot wound (58%) and 25 stab wounds (42%). The injury severity score (ISS) was > 30 in 22 patients; overall survival was 22 of 60 (36.6%); gunshot wound (GSW) survival, 5 of 35 (14%); and stab wound (SW) survival, 17 of 25 (68%). An emergency department thoracotomy was performed in 37 of 60 (61.7%) with 6 of 37 survivors (16%). CVRS: 96% mortality (25 of 26) when CVRS = 0; 67% mortality (6 of 9) when CVRS = 1-3; and 25% mortality (7 of 25) when CVRS > 4 (p < 0.001). Mechanism of injury, and presence of sinus rhythm when pericardium opened predict outcomes (p < 0.001). Anatomic site of injury and tamponade do not predict outcomes (not significant). AAST-OIS injury grade and mortality: grade IV, 31 of 60 (52%); grade V, 20 of 60 (75%), and grade VI, 6 of 60 (100%). CONCLUSIONS: Parameters measuring physiologic condition, CVRS, and mechanism of injury plus initial rhythm are significant predictors of outcomes in penetrating cardiac injuries. The need for aortic crossclamping and the inability to restore an organized rhythm or blood pressure after thoracotomy were also predictors of outcomes. The presence of pericardial tamponade was not.

Adolescent↗

Epidemiology of major trauma and trauma deaths in Los Angeles County.

BACKGROUND: Our objective was to study population-based trauma-related injuries and deaths in the county of Los Angeles and to identify trends and progress towards meeting the "Year 2000 National Health Objectives." STUDY DESIGN: We did a retrospective study for the year 1996. Data were obtained from the Trauma Registry of the Emergency Medical Services of the Department of Health Services, and the Coroner's Department of the County of Los Angeles. Traumatic injuries and deaths per 100,000 of the population were calculated according to mechanism, race, age, and gender. RESULTS: During 1996, there were 12,136 major trauma admissions in the 13 trauma centers in Los Angeles County. Another 1,929 victims died at the scene or were certified dead at nontrauma centers and were taken to the Coroner's Department (total 14,065 victims). The overall major injury rate was 151.0 per 100,000 population and the death rate was 30.9 per 100,000. The trauma death rate per 100,000 population was 56.4 for African-Americans, 33.5 for Hispanics, 26.3 for Caucasians, and 11.6 for Asians. Homicides were the leading cause of traumatic deaths (45.3%) followed by traffic accidents (31.9% of deaths). Firearms were responsible for 3,899 major injuries or deaths (41.7 per 100,000 population). The overall homicide rate per 100,000 population was 14.0, with a much higher rate for African-Americans (40.4 per 100,000) and Hispanics (18.7 per 100,000) than Caucasians (4.0 per 100,000) or Asians (3.4 per 100,000). African-American males were at very high risk for homicide (73.3 per 100,000), and in the age group 15 to 34 years, this problem reaches epidemic proportions (164.2 per 100,000). Traffic accidents accounted for 69.0 major injuries and 9.6 deaths per 100,000 people. Males were at significantly higher risk of dying in traffic accidents than females. People over 60 years of age were at significantly higher risk of traffic-accident death than younger people, for both passenger and pedestrian groups (p < 0.01). Firearm-related suicides were responsible for 4.6 deaths per 100,000 population. Caucasian males over 65 years were at much higher risk of suicide by penetrating trauma (29.5 per 100,000) than were Hispanics (6.3 per 100,000), Asians (5.4 per 100,000), or African-Americans (no deaths) in the same gender and age group. CONCLUSIONS: Trauma remains a major health problem in the county of Los Angeles. Despite the significant reduction of intentional trauma in 1996, it still exceeds national figures and is much higher than the targeted "Year 2000 National Health Objectives." Aggressive prevention strategies need to focus on the population groups at excessive risks of injury by assault, traffic accidents, and suicides.

Accidents, Traffic↗