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PubMed1994

A comprehensive human linkage map with centimorgan density. Cooperative Human Linkage Center (CHLC).

In the last few years there have been rapid advances in developing genetic maps for humans, greatly enhancing our ability to localize and identify genes for inherited disorders. Through the collaborative efforts of three large groups generating microsatellite markers and the efforts of the 110 CEPH collaborators, a comprehensive human linkage map is presented here. It consists of 5840 loci, of which 970 are uniquely ordered, covering 4000 centimorgans on the sex-averaged map. Of these loci, 3617 are polymerase chain reaction-formatted short tandem repeat polymorphisms, and another 427 are genes. The map has markers at an average density of 0.7 centimorgan, providing a resource for ready transference to physical maps and achieving one of the first goals of the Human Genome Project--a comprehensive, high-density genetic map.

Chromosome Mapping↗
PubMed2003

Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load.

Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/10(6) PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

Acquired Immunodeficiency Syndrome↗
PubMed2025

A comprehensive reference catalog of human skin DNA virome reveals novel viral diversity and microenvironmental influences.

UNLABELLED: Human skin serves as a dynamic habitat for a diverse microbiome, including a complex array of viruses whose diversity and roles are not fully understood. A total of 2,760 skin metagenomes from 6 published skin studies were collected. A skin virome catalog was constructed using standard methods in the viromics field. Viral characteristics were identified through cross-cohort meta-analysis and used to characterize viral features across different skin environments. We identified 20,927 viral sequences, which clustered into 2,873 viral operational taxonomic units (vOTUs), uncovering a substantial breadth of viral diversity on human skin. The results also highlight significant differences in viral communities that are associated with varying skin microenvironments. The oily skin is enriched in Papillomaviridae, the dry skin area is enriched in Autographiviridae and Inoviridae, and the moist skin is enriched in Herelleviridae. We also investigated the relationship between bacteriophages and bacteria on the skin surface. We found that skin bacteria such as Pseudomonas, Klebsiella, and Staphylococcus are predicted to be infected by phages from the class Caudoviricetes. This comprehensive skin DNA viral catalog significantly advances our understanding of the virome's role within the skin ecosystem. IMPORTANCE: This study presents a comprehensive reference catalog of the human skin DNA virome, constructed from 2,760 metagenomic datasets collected globally. It identified 20,927 viral sequences, with 90.85% representing previously unknown viruses, greatly expanding our understanding of skin viral diversity. The findings reveal significant differences in viral communities between distinct skin microenvironments (oily, dry, and moist) and highlight close interactions between bacteriophages and their bacterial hosts, suggesting a potential role for the virome in maintaining microbial balance and skin health. This extensive skin viral catalog constitutes a crucial resource for future epidemiological and therapeutic research, potentially facilitating the development of novel phage therapies and diagnostic markers for skin disorders.

Humans↗
PubMedDate not supplied

GEM: a proposal for a more comprehensive guideline document model using XML.

OBJECTIVE: To develop a guideline document model that includes a sufficiently broad set of concepts to be useful throughout the guideline life cycle. DESIGN: Current guideline document models are limited in that they reflect the specific orientation of the stakeholder who created them; thus, developers and disseminators often provide few constructs for conceptualizing recommendations, while implementers de-emphasize concepts related to establishing guideline validity. The authors developed the Guideline Elements Model (GEM) using XML to better represent the heterogeneous knowledge contained in practice guidelines. Core constructs were derived from the Institute of Medicine's Guideline Appraisal Instrument, the National Guideline Clearinghouse, and the augmented decision table guideline representation. These were supplemented by additional concepts from a literature review. RESULTS: The GEM hierarchy includes more than 100 elements. Major concepts relate to a guideline's identity, developer, purpose, intended audience, method of development, target population, knowledge components, testing, and review plan. Knowledge components in guideline documents include recommendations (which in turn comprise conditionals and imperatives), definitions, and algorithms. CONCLUSION: GEM is more comprehensive than existing models and is expressively adequate to represent the heterogeneous information contained in guidelines. Use of XML contributes to a flexible, comprehensible, shareable, and reusable knowledge representation that is both readable by human beings and processible by computers.

Algorithms↗
PubMed1974

Comprehensive one-day renal function testing in man.

A comprehensive one-day renal function test consisting of a single outpatient visit lasting nine hours, with a minimum of time off work or away from home, is described in detail. Although a large number of laboratory tests are performed in one day, patients usually appreciate thoroughness, and the cost is more than offset by the saving in occupancy of hospital beds and by the early and precise diagnosis of reversible aspects of renal disease. Some aspects of improved methodology, such as the sequential determination of minimum urinary pH, bicarbonate, titratable acid, ammonium, and total acid on a single sample using an automatic titrator, are given in detail. Clinical application of the comprehensive nine-hour renal function testing system is illustrated by the result sheet of a patient with analgesic nephropathy, who was shown in one day to have secondary severe renal failure (glomerular filtration rate 20% of normal for age and surface area), renal tubular acidosis of the distal gradient type (minimum urinary pH 6.20), increased urinary white cell excretion rate, hyaline casts, and absence of red cell casts, consistent with a diagnosis of analgesic nephropathy and urinary tract inflammation. Normal values with 95% range for this laboratory are also given. This testing system has been found to be very useful in investigating patients with analgesic nephropathy, renal tubular acidosis, and after renal transplantation.

Acidosis, Renal Tubular↗
PubMed1975

Auditory affective agnosia. Disturbed comprehension of affective speech.

Hughlings Jackson noted that, although some aphasic patients were unable to use propositional speech, affective speech appeared to be spared. The purpose of this experiment was to study patients with unilateral hemispheric disease in order to ascertain if there are hemispheric asymmetries in the comprehension of affective speech. Six subjects had right temporoparietal lesions (left unilateral neglect) and six subjects had left temporoparietal lesions (fluent aphasias). These subjects were presented with 32 tape recorded sentences. In 16 trials the patients were asked to judge the emotional mood of the speaker (happy, sad, angry, indifferent) and in 16 trials the patients were asked to judge the content. Line drawings containing facial expressions of the four emotions or line drawings corresponding with the four basic contents were displayed with each sentence and the patient responded by pointing. All 12 subjects made perfect scores on the content portion of the test. On the emotional portion the right hemispheric patients scored a mean of 4-17 and the left hemispheric group scored a mean 10-17. The difference between these means is significantly (P less than 0-01) and suggests that patients with right hemispheric dysfunction and neglect have a defect in the comprehension of affective speech.

Adult↗
PubMed2000

Evolution of a comprehensive tobacco control programme: building system capacity and strategic partnerships--lessons from Massachusetts.

BACKGROUND: Since the passage of a voter approved state referendum in 1992 to establish a 25 cent increase on the excise tax on cigarettes and smokeless tobacco, Massachusetts has received an average of $40 million annually for its tobacco control programme. This funding allowed Massachusetts to expand and develop its tobacco control programme to become one of the most comprehensive in the world. OBJECTIVES: The development of the Massachusetts Tobacco Control Program is outlined, focusing on three stages of development: formation, strategic partnership building, and shared leadership. METHODS: The development of management structures, programmatic infrastructure, communication and partnership networks, and advisory structures are tracked throughout the three phases. RESULTS: The use of pre-existing public health resources, implementation of a strong training component, a geographical management structure, the creation of public and private partnerships, and the development of a shared leadership model contributed to building consensus and provided the foundation for coordinated approaches to tobacco control. CONCLUSION: Other states and countries can use lessons learned from Massachusetts about the organisational development of a comprehensive tobacco control programme as they embark upon similar efforts.

Humans↗
PubMed2007

Toward a comprehensive set of asthma susceptibility genes.

Epidemiological and twin studies have demonstrated that asthma is under genetic and environmental influences. Numerous candidate gene association studies as well as genome-wide linkage scans have followed, aiming to elucidate the genetic architecture underlying this complex disease. Several promising asthma susceptibility genes were identified, and a comprehensive catalogue of these genes seems a realistic goal within 5 to 10 years. However, a key challenge is to understand the combination of genes and environmental factors that gives rise to the disease in a specific individual. Currently, most of the reports of asthma susceptibility genes are either preliminary or controversial, with little knowledge about the genetic mechanisms leading to abnormal function of the gene that promotes the development of asthma. Replications of published associations are relatively few. Many factors, including the inherent complexity of asthma as well as methodological issues, can explain these inconsistencies. Promising genetic tools are emerging with the completion of the International HapMap Project that will increase the scope of gene-discovery investigations. It is hoped that these tools, combined with validation studies in additional populations, will enable the creation of a comprehensive catalogue of susceptibility genes for asthma. Notwithstanding the difficulties in making sense of the vast amount of new genetic data, we already see the emergence of new biological pathways of atopy, airway remodeling, and asthma that may lead to novel therapeutic approaches.

Asthma↗
PubMed2001

Sentence and text comprehension: roles of linguistic structure.

Readers and listeners use linguistic structure in comprehending sentences and texts. We review research, mostly published in the past five years, that addresses the question of how they use it. We consider effects of syntactic, lexical, prosodic, morphological, semantic, and discourse structure, as well as reviewing research on how discourse context and frequency of experience, the contents of long-term memory, and the mental models being constructed by a reader or listener affect sentence and text comprehension. We point out areas of theoretical debate including depth-first versus breadth-first models of parsing and memory-based versus constructionist models of discourse comprehension, attempt to show how the empirical effects we review bear on such theoretical questions, and discuss how new lines of research, including research on languages other than English, may enrich the discussion of these questions.

Cognition↗
PubMed2002

Neuroimaging studies of language production and comprehension.

The 1990s were dubbed the "Decade of the Brain." During this time there was a marked increase in the amount of neuroimaging work observing how the brain accomplishes many tasks, including the processing of language. In this chapter we review the past 15 years of neuroimaging research on language production and comprehension. The findings of these studies indicate that the processing involved in language use occurs in diffuse brain regions. These regions include Broca's and Wernicke's areas, primary auditory and visual cortex, and frontal regions in the left hemisphere, as well as in the right hemisphere homologues to these regions. We conclude the chapter by discussing the future of neuroimaging research into language production and comprehension.

Brain Mapping↗
PubMed2000

Pulmonary embolism: comprehensive diagnosis by using electron-beam CT for detection of emboli and assessment of pulmonary blood flow.

PURPOSE: To comprehensively assess thoracic anatomy and pulmonary microcirculation in pulmonary embolism by using computed tomographic (CT) angiography of the pulmonary arteries combined with functional CT imaging of blood flow. MATERIALS AND METHODS: Twenty-two patients suspected of having acute pulmonary embolism underwent contrast material-enhanced thin-section electron-beam CT angiography of the pulmonary arteries. In addition, in each patient, a dynamic multisection blood flow CT study was performed on a 7.6-cm lung volume with electrocardiographic gating. Pulmonary blood flow was calculated, and perfusion parameters were visualized on color-coded maps. The color-coded maps and CT angiograms were independently evaluated, segment by segment, by two readers for perfusion deficits and the presence of clots, respectively. The results were compared. RESULTS: Mean pulmonary blood flow was 0.63 mL/min/mL in the occluded segments versus 2.27 mL/min/mL in the nonoccluded segments (P: =.001). The sensitivity and specificity of perfusion maps for the presence of segmental pulmonary embolism compared with those of CT angiography were 75.4% and 82.3%, respectively, with positive and negative predictive values of 79.6% and 84.7%, respectively. The false-negative findings were caused mainly by partial occlusion of vessels. In eight patients, a substantial alternative or additional pathologic entity was diagnosed. CONCLUSION: By combining CT angiography and dynamic CT imaging, a comprehensive and noninvasive diagnosis of thoracic structure and function is feasible with a single modality.

Acute Disease↗
PubMed2006

[Evaluation of the efficacy of a comprehensive programme of secondary prevention of cardiovascular disease in primary care: the PREseAP Study].

OBJECTIVES: To assess the efficacy of a comprehensive secondary prevention programme to reduce morbidity and mortality in patients who have suffered a cardiovascular (CV) event; to control CV risk factors and prophylactic treatment in order to prevent recurrence; and to improve the quality of life of patients with cardiovascular disease. DESIGN: Randomised, pragmatic, open clinical trial in primary care. SETTING: A total of 42 primary care centres of 8 different areas in Spain. PARTICIPANTS: Men and women below 86 years old, diagnosed with coronary disease and/or stroke and/or peripheral vascular disease in the preceding year, and who have no serious or terminal disease. INTERVENTION: Primary care centres will be randomised to following usual care (control group), or to following a comprehensive programme of secondary prevention (intervention group). MAIN MEASUREMENTS: Cardiovascular fatal events, cardiovascular non-fatal events, total mortality and health-related quality of life (SF-36).

Adult↗
PubMedDate not supplied

Ethics and comprehensive diagnosis.

This paper briefly reviews basic concepts of ethics, including its meanings and dimensions and its relationship to culture. It then examines the ethical bases of medicine and psychiatry. Of particular relevance here is the connection between ethics as concern for totality and the fundamentals of health and healing. Next, the ethical bases and implications of clinical diagnosis are considered. Finally, the paper outlines the features of a comprehensive diagnostic model and explicates how ethics is linked to the integrative nature of comprehensive diagnosis and its therapeutic purpose.

Ethics, Medical↗
PubMedDate not supplied

A randomised controlled clinical trial on the additional effect of hypnosis in a comprehensive treatment programme for in-patients with conversion disorder of the motor type.

BACKGROUND: The primary aim of this study was threefold: (1) to examine the additional effects of hypnosis aimed at symptom reduction, using symptom-oriented and expression- and insight-oriented techniques in a comprehensive clinical treatment programme for in-patients with a persistent conversion disorder of the motor type; (2) to assess whether the level of hypnotisability was predictive of treatment outcome, and (3) to explore the efficacy of the total clinical treatment programme. METHODS: The study population consisted of 45 in-patients between 18 and 65 years of age meeting the DSM-III-R criteria for conversion disorder of the motor type or somatisation disorder with motor conversion symptoms. A randomised controlled clinical trial was undertaken. The primary outcome measures were the Video Rating Scale for Motor Conversion Symptoms, the D(isabilities) code items from the International Classification of Impairments, Disabilities and Handicaps and the Symptom Checklist-90. Measures of the credibility of treatment and patient expectations of treatment outcome were used as manipulation checks. Hypnotisability was measured using the Stanford Hypnotic Clinical Scale. RESULTS: Significant treatment results for all outcome measures were found for the total sample. These effects proved to be clinically significant. The use of hypnosis had no additional effect on treatment outcome. Hypnotisability was not predictive of treatment outcome. CONCLUSION: A comprehensive treatment programme, either with or without hypnosis, can be worthwhile for patients with long-standing conversion symptoms.

Adolescent↗
PubMed2005

Psychological and quality-of-life outcomes from a comprehensive stress reduction and lifestyle program in patients with coronary artery disease: results of a randomized trial.

BACKGROUND: Stress reduction and comprehensive lifestyle modification programs have improved atherosclerosis and cardiac risk factors in earlier trials. Little is known about the impact of such programs on quality-of-life (QoL) and psychological outcomes. Given recent significant improvements in cardiac care, we evaluated the current benefit of stress reduction/lifestyle modification on QoL and emotional distress in patients with coronary artery disease (CAD). METHODS: 101 patients (59.4 +/- 8.6 years, 23 female) with CAD were randomized to a 1-year lifestyle/stress management program (n = 48) or written advice (n = 53). QoL and psychological outcomes were assessed with the SF-36, Beck Depression, Spielberger State/Trait Anxiety, Spielberger State/Trait Anger and Perceived Stress Inventories. Group repeated-measures analyses of variance were performed for all measures. RESULTS: Adherence to the program was excellent (daily relaxation practice 39 +/- 5 vs. 5 +/- 8 min, respectively; p < 0.001). Both groups improved comparably in most dimensions of QoL, and significantly greater improvements for the lifestyle group were found for physical function and physical sum score (p = 0.046 and p = 0.045). Depression, anxiety, anger and perceived stress were reduced similarly in both groups. However, intervention x gender interaction effects revealed greater benefits among women in the lifestyle intervention vs. advice group for depression and anger (p = 0.025 and p = 0.040), but no effects for men. CONCLUSIONS: A comprehensive lifestyle modification and stress management program did not improve psychological outcomes in medically stable CAD patients. The program did appear to confer psychological benefits for women but not men. Further trials should investigate gender-related differences in coronary patient responses to behavioral interventions.

Aged↗
PubMed1997

Clinical findings, status of care, comprehensive quality of life, daily life therapy and treatment at home in patients with Parkinson's disease.

We analyzed patients with Parkinson's disease from various aspects such as clinical findings, the degree of independence in daily life, care environment, quality of life (QOL) and treatment at home. The subjects were 104 in- and outpatients (47 males and 57 females) seen at our hospital. The mean age was 69.85 years in the males and 70.35 years in the females. The disease most frequently developed at the age of 60-69 years and the disease duration was 5 years or more in 52 patients. Rigidity was the most common symptom (91 patients), followed by gait disturbance (n = 87) and tremor (n = 86). Levodopa/carbidopa was the drug most frequently used (77 patients). The number of patients treated by combination drug therapy increased with the duration of disease. Concerning the degree of independence in daily life, assistance was often necessary in bathing, dressing and undressing, toileting and walking. In particular, total assistance was necessary in patients with Hoehn-Yahr stage-IV and V disease. The comprehensive QOL was the lowest in terms of social activities, hobbies and leisure activities, followed in order by work and subjective QOL. QOL decreased in each item with the severity of the disease. Treatment at home was performed for 19 patients, of whom 11 are still being treated by our staff. Treatment at home combined with persons who care for the patient and in cooperation with other welfare resources may improve the patient's QOL. In diseases that require long-term care such as Parkinson's disease, a comprehensive care management system should be established from the aspect of the patient's QOL.

Activities of Daily Living↗
PubMed1987

Comprehensive management of persistent somatization: an innovative inpatient program.

Psychiatry has been largely unsuccessful in developing effective treatment strategies for patients with chronic somatization. They continue to utilize a disproportionate share of health care resources and experience personal distress and significant social and occupational dysfunction. The Psychosomatic Medicine Unit at the Clarke Institute of Psychiatry is attempting to treat these patients with a comprehensive treatment program that takes into account the multifactorial etiology of the disturbance. The unit is in a tertiary care facility and the patient population is heterogeneous with respect to the underlying psychiatric diagnosis and the duration of symptoms. All patients are significantly dysfunctional and have typically failed other treatment approaches. The treatment process begins with an assessment phase in which the patient is comprehensively evaluated from the physical and psychiatric perspectives. The rehabilitation phase consists of a variety of treatment modalities including group programs in goal-setting, life skills and interpersonal relations, group therapy, individual psychotherapy, family therapy, occupational therapy and vocational rehabilitation, biofeedback and physiotherapy. Psychotropic medications play an important role in some patients. This paper will describe the unit and its program in detail.

Combined Modality Therapy↗
PubMed2003

Expanded modes of tissue plasminogen activator delivery in a comprehensive stroke center increases regional acute stroke interventions.

BACKGROUND AND PURPOSE: We sought to evaluate whether a comprehensive stroke center could work with regional hospitals to increase the use of tissue plasminogen activator (tPA) in acute stroke. METHODS: In 30 months, 142 patients seen at the Mid America Brain and Stroke Institute received tPA. Site of presentation, protocol selection, and outcomes were analyzed. RESULTS: We found that 18.2% (142 of 781) of all ischemic strokes received tPA. Of those, 70% (99 of 142) were transferred from hospitals within 100 miles of Kansas City (Mo). Mortality rate was 12.7% (18 of 142). Symptomatic hemorrhage rate was 9.2%. CONCLUSIONS: A comprehensive stroke center can serve as a hub for a regional network and increase the number of stroke interventions with acceptable outcomes.

Acute Disease↗