Showing papers by "University of Texas Health Science Center at Houston published in 2001"
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
22,269 citations
Royal College of Physicians1, University of Cambridge2, University of California, San Francisco3, University of Graz4, Icahn School of Medicine at Mount Sinai5, National Institutes of Health6, University of British Columbia7, VU University Amsterdam8, National Multiple Sclerosis Society9, Lund University10, University of Arizona11, University College London12, University of California, Irvine13, Mayo Clinic14, University of Texas Health Science Center at Houston15
TL;DR: The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including “monosymptomatic” disease suggestive of MS, disease with a typical relapsing‐remitting course, and disease with insidious progression, without clear attacks and remissions.
Abstract: The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."
6,720 citations
TL;DR: STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed and demonstrates the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer.
Abstract: Background BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia (CML). Since tyrosine kinase activity is essential to the transforming function of BCR-ABL, an inhibitor of the kinase could be an effective treatment for CML. Methods We conducted a phase 1, dose-escalating trial of STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR-ABL tyrosine kinase. STI571 was administered orally to 83 patients with CML in the chronic phase in whom treatment with interferon alfa had failed. Patients were successively assigned to 1 of 14 doses ranging from 25 to 1000 mg per day. Results Adverse effects of STI571 were minimal; the most common were nausea, myalgias, edema, and diarrhea. A maximal tolerated dose was not identified. Complete hematologic responses were observed in 53 of 54 patients treated with daily doses of 300 mg or more and typically occurred in the first four weeks of therapy. Of the 54 patients treated with doses of 300 mg or more, cytogenetic res...
5,037 citations
TL;DR: The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL.
Abstract: Background BCR-ABL, a constitutively activated tyrosine kinase, is the product of the Philadelphia (Ph) chromosome. This enzyme is present in virtually all cases of chronic myeloid leukemia (CML) throughout the course of the disease, and in 20 percent of cases of acute lymphoblastic leukemia (ALL). On the basis of the substantial activity of the inhibitor in patients in the chronic phase, we evaluated STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR-ABL tyrosine kinase, in patients who had CML in blast crisis and in patients with Ph-chromosome–positive ALL. Methods In this dose-escalating pilot study, 58 patients were treated with STI571; 38 patients had myeloid blast crisis and 20 had ALL or lymphoid blast crisis. Treatment was given orally at daily doses ranging from 300 to 1000 mg. Results Responses occurred in 21 of 38 patients (55 percent) with a myeloid-blast-crisis phenotype; 4 of these 21 patients had a complete hematologic response. Of 20 patients with lymphoid blast crisis ...
2,724 citations
TL;DR: Gross-total tumor resection is associated with longer survival in patients with GBM, especially when other predictive variables are favorable.
Abstract: Object. The extent of tumor resection that should be undertaken in patients with glioblastoma multiforme (GBM) remains controversial. The purpose of this study was to identify significant independent predictors of survival in these patients and to determine whether the extent of resection was associated with increased survival time. Methods. The authors retrospectively analyzed 416 consecutive patients with histologically proven GBM who underwent tumor resection at the authors' institution between June 1993 and June 1999. Volumetric data and other tumor characteristics identified on magnetic resonance (MR) imaging were collected prospectively. Conclusions. Five independent predictors of survival were identified: age, Karnofsky Performance Scale (KPS) score, extent of resection, and the degree of necrosis and enhancement on preoperative MR imaging studies. A significant survival advantage was associated with resection of 98% or more of the tumor volume (median survival 13 months, 95% confidence interval [C...
2,641 citations
TL;DR: Before treatment studies on impulsivity can move forward, measures of impulsivity that capture the core aspects of this behavior need to be refined and tested on the basis of an ideologically neutral model of impulsiveness.
Abstract: OBJECTIVE: The authors discuss the relationship of impulsivity to psychiatric disorders and present selected hypotheses regarding the reasons for these relationships. METHOD: Previous research has shown significantly higher levels of impulsivity among patients with conduct disorder, personality disorders, substance use disorders, and bipolar disorder, compared to other psychiatric patients or healthy comparison subjects. A literature review of the theoretical bases of the relationship between these disorders and impulsivity is presented. Measurements of impulsivity and treatment options are discussed in relation to the physiology of impulsivity and the disorders in which it is a prominent feature. RESULTS: Impulsivity, as defined on the basis of a biopsychosocial approach, is a key feature of several psychiatric disorders. Behavioral and pharmacological interventions that are effective for treating impulsivity should be incorporated into treatment plans for these disorders. CONCLUSIONS: The high comorbidi...
2,277 citations
TL;DR: Treatment with hypothermia, with the body temperature reaching 33 degrees C within eight hours after injury, is not effective in improving outcomes in patients with severe brain injury.
Abstract: Background Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies, but the results were not definitive. To study this issue, we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury. Methods The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were randomly assigned to be treated with hypothermia (body temperature, 33°C), which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling, or normothermia. All patients otherwise received standard treatment. The primary outcome measure was functional status six months after the injury. Results The mean age of the patients and the type and severity of injury in the two treatment groups were similar. The mean (±SD) time from injury to randomization was 4.3±1.1 hours in the hypothermia group and 4.1±1.2 hours in the normothermia group, a...
1,305 citations
TL;DR: From different sources of evidence, two inescapable conclusions emerge: Mastering the alphabetic principle is essential to becoming proficient in the skill of reading, and methods that teach this principle directly are more effective than those that do not.
Abstract: This monograph discusses research, theory, and prac- tice relevant to how children learn to read English. After an initial overview of writing systems, the discussion summarizes research from developmental psychology on children's lan- guage competency when they enter school and on the nature of early reading development. Subsequent sections review theo- ries of learning to read, the characteristics of children who do not learn to read (i.e., who have developmental dyslexia), re- search from cognitive psychology and cognitive neuroscience on skilled reading, and connectionist models of learning to read. The implications of the research findings for learning to read and teaching reading are discussed. Next, the primary methods used to teach reading (phonics and whole language) are summarized. The final section reviews laboratory and classroom studies on teaching reading. From these different sources of evidence, two inescapable conclusions emerge: (a) Mastering the alphabetic principle (that written symbols are associated with phonemes) is essential to becoming proficient in the skill of reading, and (b) methods that teach this principle directly are more effective than those that do not (especially for children who are at risk in some way for having difficulty learning to read). Using whole-language activities to supple- ment phonics instruction does help make reading fun and meaningful for children, but ultimately, phonics instruction is critically important because it helps beginning readers under- stand the alphabetic principle and learn new words. Thus, ele- mentary-school teachers who make the alphabetic principle explicit are most effective in helping their students become skilled, independent readers.
869 citations
TL;DR: The results further strengthen the role of CRP in the pathogenesis of vascular inflammation and, likely, atherosclerosis and provide a crucial insight into a novel mechanism of action of anti-atherosclerosis drugs such as simvastatin and fenofibrate.
Abstract: Background—C-reactive protein (CRP) induces adhesion molecule expression by endothelial cells. However, the effects of CRP on chemokine expression by endothelial cells are not known. Methods and Re...
831 citations
Journal Article•
TL;DR: The MDADI is the first validated and reliable self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the QOL of patients with head and neck cancer.
Abstract: Objective To design a reliable and validated self-administered questionnaire whose purpose is to assess dysphagia's effects on the quality of life (QOL) of patients with head and neck cancer. Design Cross-sectional survey study. Methods Focus groups were convened for questionnaire development and design. The M. D. Anderson Dysphagia Inventory (MDADI) included global, emotional, functional, and physical subscales. One hundred consecutive adult patients with a neoplasm of the upper aerodigestive tract who underwent evaluation by our Speech Pathology team completed the MDADI and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Speech pathologists completed the Performance Status Scale for each patient. Validity and reliability properties were calculated. Analysis of variance was used to assess how well the MDADI discriminated between groups of patients. Results The internal consistency reliability of the MDADI was calculated using the Cronbach alpha coefficient. The Cronbach alpha coefficients of the MDADI subscales ranged from 0.85 to 0.93. Test-retest reliability coefficients of the subscales ranged from 0.69 to 0.88. Spearman correlation coefficients between the MDADI subscales and the SF-36 subscales demonstrated construct validity. Patients with primary tumors of the oral cavity and oropharynx had significantly greater swallowing disability with an adverse impact on their QOL compared with patients with primary tumors of the larynx and hypopharynx (P Conclusions The MDADI is the first validated and reliable self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the QOL of patients with head and neck cancer. Standardized questionnaires that measure patients' QOL offer a means for demonstrating treatment impact and improving medical care. The development and validation of the MDADI and its use in prospective clinical trials allow for better understanding of the impact of treatment of head and neck cancer on swallowing and of swallowing difficulty on patients' QOL.
783 citations
Journal Article•
TL;DR: Empirical studies should be conducted on the protective effects of immigrant status, identification with a subculture, interaction between acculturation and socioeconomic status, and supportive aspects of Hispanic culture on the basis of evidence of an Hispanic paradox.
Abstract: Purpose This paper reviews the literature on the nature of the Hispanic paradox and the major explanations provided for it. We conclude by suggesting directions for future research. DATA IDENTIFICATION AND STUDY SELECTION: Articles were selected by a systematic review procedure using Medline (1966 through 1999) and Sociological Abstracts (1963 through 1999), as well as focused searches on specific diseases or factors believed to influence Hispanic health. Findings For the past twenty years there has been widespread evidence of an Hispanic paradox in the United States, in which most Hispanic groups are characterized by low socioeconomic status, but better than expected health and mortality outcomes. A closer look reveals variations by age, gender, Hispanic subgroup, acculturation, country of birth, and cause of death. Possible under-reporting of Hispanic deaths, "salmon bias" and healthy migrant effects, and risk profile may contribute to, but do not explain, the paradox. The reasons for this paradox are likely to be multifactorial and social in origin. Conclusions Empirical studies should be conducted on the protective effects of immigrant status, identification with a subculture, interaction between acculturation and socioeconomic status, and supportive aspects of Hispanic culture.
Journal Article•
TL;DR: Children, especially preterm children, showed faster cognitive growth when mothers were consistently responsive, and the importance of consistent responsiveness, defined by an affective-emotional construct, was evident even when a broader constellation of parenting behaviors was considered.
Abstract: The role of early versus ongoing maternal responsiveness in predicting cognitive and social development was examined in home visits for mothers, full-term children (n = 103), and medically low-risk (n = 102) and high-risk (n = 77) preterm children at 5 ages. There were 4 maternal clusters based on warm and contingent responsiveness behaviors observed early (at 6, 12, and 24 months) and late (at 3 and 4 years): high early, high late; high early, low late; low early, moderate late; and low early, low late. Children, especially preterm children, showed faster cognitive growth when mothers were consistently responsive. Social growth was similar in the consistently responsive (high-high) and the early-responsive inconsistent (high-low) clusters, but greater deceleration at 4 years among children with mothers in the inconsistent cluster refuted the notion of a unique role for early responsiveness. The importance of consistent responsiveness, defined by an affective-emotional construct, was evident even when a broader constellation of parenting behaviors was considered.
TL;DR: In the human heart, metabolic genes exist as constitutive and inducible forms and the failing adult heart reverts to a fetal metabolic gene profile by downregulating adult gene transcripts rather than by upregulating fetal genes.
Abstract: Background— Previous studies suggest that the failing heart reactivates fetal genes and reverts to a fetal pattern of energy substrate metabolism. We tested this hypothesis by examining metabolic gene expression profiles in the fetal, nonfailing, and failing human heart. Methods and Results— Human left ventricular tissue (apex) was obtained from 9 fetal, 10 nonfailing, and 10 failing adult hearts. Using quantitative reverse transcription-polymerase chain reaction, we measured transcript levels of atrial natriuretic factor, myosin heavy chain-α and -β, and 13 key regulators of energy substrate metabolism, of which 3 are considered “adult” isoforms (GLUT4, mGS, mCPT-I) and 3 are considered “fetal” isoforms (GLUT1, lGS, and lCPT-I), primarily through previous studies in rodent models. Compared with the nonfailing adult heart, steady-state mRNA levels of atrial natriuretic factor were increased in both the fetal and the failing heart. The 2 myosin heavy chain isoforms showed the highest expression level in th...
TL;DR: These findings have strong clinical relevance as it has recently been shown that after injury to the motor cortex, as might occur in stroke, post‐injury behavioral experience may play an adaptive role in modifying the functional organization of the remaining, intact cortical tissue.
Abstract: Based upon neurophysiologic, neuroanatomic, and neuroimaging studies conducted over the past two decades, the cerebral cortex can now be viewed as functionally and structurally dynamic. More specifically, the functional topography of the motor cortex (commonly called the motor homunculus or motor map), can be modified by a variety of experimental manipulations, including peripheral or central injury, electrical stimulation, pharmacologic treatment, and behavioral experience. The specific types of behavioral experiences that induce long-term plasticity in motor maps appear to be limited to those that entail the development of new motor skills. Moreover, recent evidence demonstrates that functional alterations in motor cortex organization are accompanied by changes in dendritic and synaptic structure, as well as alterations in the regulation of cortical neurotransmitter systems. These findings have strong clinical relevance as it has recently been shown that after injury to the motor cortex, as might occur in stroke, post-injury behavioral experience may play an adaptive role in modifying the functional organization of the remaining, intact cortical tissue.
TL;DR: The use of the nematode Caenorhabditis elegans is demonstrated as a facile and inexpensive model host for several Gram-positive human bacterial pathogens and an E. faecalis virulence factor, ScrB, which is relevant to mammalian pathogenesis is exploited.
Abstract: We demonstrate the use of the nematode Caenorhabditis elegans as a facile and inexpensive model host for several Gram-positive human bacterial pathogens. Enterococcus faecalis, Streptococcus pneumoniae, and Staphylococcus aureus, but not Bacillus subtilis, Enterococcus faecium, or Streptococcus pyogenes, kill adult C. elegans. Focusing our studies on the enterococcal species, we found that both E. faecalis and E. faecium kill C. elegans eggs and hatchlings, although only E. faecalis kills the adults. In the case of adults, a low inoculum of E. faecalis grows to a high titer in the C. elegans intestine, resulting in a persistent infection that cannot be eradicated by prolonged feeding on E. faecium. Interestingly, a high titer of E. faecium also accumulates in the nematode gut, but does not affect the longevity of the worms. Two E. faecalis virulence-related factors that play an important role in mammalian models of infection, fsr, a putative quorum-sensing system, and cytolysin, are also important for nematode killing. We exploit the apparent parallels between Gram-positive infection in simple and more complex organisms by using the nematode to identify an E. faecalis virulence factor, ScrB, which is relevant to mammalian pathogenesis.
TL;DR: The authors designed a treatment to systematically increase exposure to positive activities, and thereby improve affect and corresponding cognitions and provides the treatment in manual form to be utilized by patients in therapy.
Abstract: The brief behavioral activation treatment for depression is a simple, cost-effective method for treating depression Based on basic behavioral theory and recent evidence that the behavioral component may be the active mechanism of change in cognitive-behavioral treatments of clinical depression, the authors designed a treatment to systematically increase exposure to positive activities, and thereby improve affect and corresponding cognitions This article describes the rationale for the treatment and provides the treatment in manual form to be utilized by patients in therapy
TL;DR: This analysis presents an exhaustive inventory of an eukaryotic ribosome at the molecular level, with mainly rRNA contributing to its molecular environment.
TL;DR: This analysis shows that, in patients with HIV-1 infection, a single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS.
Abstract: Background From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS. Methods Genotyping of HLA class I loci was performed for 850 patients who seroconverted and had known dates of HIV-1 infection. Survival analyses with respect to the rate of progression to AIDS were performed to identify the effects of closely related HLA-B*35 subtypes with different peptide-binding specificities. Results HLA-B*35 subtypes were divided into two groups according to peptide-binding specificity: the HLA-B*35-PY group, which consists primarily of HLA-B*3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px group, which also binds epitopes with proline in position 2 but can bind several different amino acids (not including tyrosine) in position 9. The influence of HLA-B*35 in accelerating progression to AIDS was completely attributable to HLA-B*35-Px alleles, some of which differ from HLA-B*35-PY alleles by only one amino acid residue. Conclusions This analysis shows that, in patients with HIV-1 infection, a single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS. The different consequences of HLA-B*35-PY and HLA-B*35-Px in terms of disease progression highlight the importance of the epitope specificities of closely related class I molecules in the immune defense against HIV-1.
TL;DR: The results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP, and create a risk profile for SUDEP that may help direct preventative efforts.
Abstract: Objective: To determine incidence of and risk factors for sudden unexpected death in epilepsy (SUDEP). Methods: Three epilepsy centers enrolled 4,578 patients and prospectively followed these patients for 16,463 patient-years. The cohort was screened for death annually. Deaths were investigated to determine whether SUDEP occurred. Potential risk factors were compared in SUDEP cases and in controls enrolled contemporaneously at the same center. Results: Incidence of SUDEP was 1.21/1,000 patient-years and was higher among women (1.45/1,000) than men (0.98/1,000). SUDEP accounted for 18% of all deaths. Occurrence of tonic-clonic seizures, treatment with more than two anticonvulsant medications, and full-scale IQ less than 70 were independent risk factors for SUDEP. The number of tonic-clonic seizures was a risk factor only in women. The presence of cerebral structural lesions and use of psychotropic drugs at the last visit were not risk factors for SUDEP in this cohort. Subtherapeutic anticonvulsant levels at the last visit were equally common in the two groups. No particular anticonvulsant appeared to be associated with SUDEP. Conclusions: These results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP. This information creates a risk profile for SUDEP that may help direct preventative efforts.
TL;DR: In this article, the authors argue that the components of effective reading instruction are the same whether the focus is prevention or intervention: phonemic awareness and phonemic decoding skills, fluency in word recognition and text processing, construction of meaning, vocabulary, spelling, and writing.
Abstract: The components of effective reading instruction are the same whether the focus is prevention or intervention: phonemic awareness and phonemic decoding skills, fluency in word recognition and text processing, construction of meaning, vocabulary, spelling, and writing. Findings from evidence-based research show dramatic reductions in the incidence of reading failure when explicit instruction in these components is provided by the classroom teacher. To address the needs of children most at risk of reading failure, the same instructional components are relevant but they need to be made more explicit and comprehensive, more intensive, and more supportive in small-group or one-on-one formats. The argument is made that by coordinating research evidence from effective classroom reading instruction with effective small-group and one-on-one reading instruction we can meet the literacy needs of all children.
TL;DR: These studies provide convincing support for the hypothesis that superoxide generation in general, and NADPH oxidase in particular, have a requisite role in atherosclerotic lesion formation, and they provide a rationale for further studies to dissect the contributions of ROS to vascular lesions formation.
Abstract: NADPH oxidase is upregulated in smooth muscle cells (SMCs) in response to growth factor stimulation, concomitant with increased reactive oxygen species (ROS) production. We investigated the role of ROS production by NADPH oxidase in SMC responses to growth factors and in atherosclerotic lesion formation in ApoE(-/-) mice. SMCs from wild-type, p47phox(-/-), and gp91phox(-/-) mice differed markedly with respect to growth factor responsiveness and ROS generation. p47phox(-/-) SMCs had diminished superoxide production and a decreased proliferative response to growth factors compared with wild-type cells, whereas the response of gp91phox(-/-) SMCs was indistinguishable from that of wild-type SMCs. The relevance of these in vitro observations was tested by measuring atherosclerotic lesion formation in genetically modified (wild-type, p47phox(-/-), ApoE(-/-), and ApoE(-/-)/p47phox(-/-)) mice. ApoE(-/-)/p47phox(-/-) mice had less total lesion area than ApoE(-/-) mice, regardless of whether mice were fed standard chow or a high-fat diet. Together, these studies provide convincing support for the hypothesis that superoxide generation in general, and NADPH oxidase in particular, have a requisite role in atherosclerotic lesion formation, and they provide a rationale for further studies to dissect the contributions of ROS to vascular lesion formation.
TL;DR: The rationale behind beliefs that the gut can be both an instigator and a victim of MOF are provided and a brief overview of the ongoing research projects in the TRC at UTHMS is provided.
Abstract: Despite intensive investigation, the pathogenesis of post-injury multiple organ failure (MOF) remains elusive. Laboratory and clinical research strongly suggests that the gastrointestinal tract (i.e., the gut) plays a pivotal pathogenic role. Since its inception in 1988, the Trauma Research Center (TRC) at the University of Texas-Houston Medical School (UTHMS) has focused its efforts on elucidating the role of the gut in post-injury MOF. On the basis of our observations and those of others, we believe that 1) shock with resulting gut hypoperfusion is an important inciting event, 2) the reperfused gut is a source of proinflammatory mediators that can amplify the early systemic inflammatory response syndrome (SIRS) and thus contribute to early MOF, 3) early gut hypoperfusion causes an ileus in both the stomach and small bowel that sets the stage for progressive gut dysfunction so that the proximal gut becomes a reservoir for pathogens and toxins that contribute to late sepsis-associated MOF, and 4) late infections cause further worsening of this gut dysfunction. Thus, the gut can be both an instigator and a victim of MOF. The purpose of this article is to provide the rationale behind these beliefs and to provide a brief overview of the ongoing research projects in the TRC at UTHMS.
TL;DR: Tween reported skin damage and known patterns of progression to assist physicians in the recognition of injuries and factors that can help improve patient care are identified.
Abstract: tween reported skin damage and known patterns of progression to assist physicians in the recognition of these injuries. We also identify factors that can help improve patient care. Fundamental Facts About Skin Injury Historical Background
TL;DR: Diffuse coronary atherosclerosis without focal stenosis at angiography causes a graded, continuous pressure fall along arterial length, which contributes to myocardial ischemia and has consequences for decision-making during percutaneous coronary interventions.
Abstract: Background Coronary arteries without focal stenosis at angiography are generally considered non–flow-limiting. However, atherosclerosis is a diffuse process that often remains invisible at angiography. Accordingly, we hypothesized that in patients with coronary artery disease, nonstenotic coronary arteries induce a decrease in pressure along their length due to diffuse coronary atherosclerosis. Methods and Results Coronary pressure and fractional flow reserve (FFR), as indices of coronary conductance, were obtained from 37 arteries in 10 individuals without atherosclerosis (group I) and from 106 nonstenotic arteries in 62 patients with arteriographic stenoses in another coronary artery (group II). In group I, the pressure gradient between aorta and distal coronary artery was minimal at rest (1±1 mm Hg) and during maximal hyperemia (3±3 mm Hg). Corresponding values were significantly larger in group II (5±4 mm Hg and 10±8 mm Hg, respectively; both P<0.001). The FFR was near unity (0.97±0.02; range, 0.92 to...
TL;DR: This study demonstrates that the use of haplotypes can significantly improve the power and robustness of mapping disease genes and derive the analytical tools based on standard chi-square statistics to directly investigate and compare the power between multilocus haplotypes and single marker LD tests.
Abstract: The genetic dissection of complex diseases represents a formidable challenge for modern human genetics. Recently, it has been suggested that linkage disequilibrium (LD) based methods will be a powerful approach for delineating complex disease genes. Most proposed LD test statistics search for association between a single marker and a putative trait locus. However, the power of a single marker association test may suffer because LD information contained in flanking markers is ignored. Intuitively, haplotypes (which can be regarded as a collection of ordered markers) may be more powerful than individual, unorganised markers. In this study, we derive the analytical tools based on standard chi-square statistics to directly investigate and compare the power between multilocus haplotypes and single marker LD tests. More specifically, novel formulas are obtained in order to calculate expected haplotype frequencies of unlimited size. This study demonstrates that the use of haplotypes can significantly improve the power and robustness of mapping disease genes. Additionally, we detail how the power of haplotype based association tests are affected by important population genetic parameters such as the genetic distance between markers and disease locus, mode of disease inheritance, age of trait causing mutation, frequency of associated marker allele, and level of initial LD. Finally, published data from the Hereditary Hemochromatosis disease region is used to illustrate the utility of haplotypes.
TL;DR: It is recommended that all pregnant women be screened for the presence of bacteriuria at their first prenatal visit because as many as one third will experience a recurrence of urinary tract infections.
TL;DR: It is shown that impulsivity is a significant predictor of cocaine use and treatment retention, and suggests the need for targeting impulsivity in cocaine dependence treatment.
TL;DR: Emergent TCD TIBI classification correlates with initial stroke severity, clinical recovery, and mortality in IV-tPA–treated stroke patients and a flow-grade improvement correlated with clinical improvement.
Abstract: Background and Purpose—TIMI angiographic classification measures coronary residual flow and recanalization. We developed a Thrombolysis in Brain Ischemia (TIBI) classification by using transcranial Doppler (TCD) to noninvasively monitor intracranial vessel residual flow signals. We examined whether the emergent TCD TIBI classification correlated with stroke severity and outcome in patients treated with intravenously administered tPA (IV-tPA). Methods—TCD examination occurred acutely and on day 2. TIBI flows were determined at distal MCA and basilar artery depths, depending on occlusion site. TIBI waveforms were graded as follows: 0, absent; 1, minimal; 2, blunted; 3, dampened; 4, stenotic; and 5, normal. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours after administration of tPA. Results—One hundred nine IV tPA patients were studied. Mean±SD age was 68±16 years; median NIHSS score before administration of tPA (pre-tPA) was 17.5. The tPA bolus was administer...
Journal Article•
TL;DR: COX-2 overexpression appears to portend a shorter survival among patients with early stage non-small cell lung cancer, like RAR-beta positivity, which indicates a poor prognosis.
Abstract: Cyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid to prostaglandins, is overexpressed in a variety of different tumors, including those of the colon, pancreas, lung, and head and neck. We used in situ hybridization with a digoxgenin-labeled COX-2 antisense riboprobe to assess the presence of strong or intermediate versus weak or absent COX-2 expression in specimens from 160 patients with stage I non-small cell lung cancer (NSCLC). Of these, 3 specimens had strong expression, 69 had intermediate expression of COX-2, 24 had weak expression, and 64 had no detectable COX-2. The strength of COX-2 expression was associated with a worse overall survival rate (P = 0.001) and a worse disease-free survival rate (P = 0.022). The median survival times for the strong, intermediate or weak, and null COX-2 expressors were 1.04, 5.50, and 8.54 years, respectively. Interestingly, all three specimens with strong COX-2 expression came from patients who died within 18 months. Retinoic acid receptor β (RAR-β) is a nuclear retinoid receptor whose expression is frequently lost in aerodigestive tract carcinogenesis. We previously demonstrated that expression of RAR-β in stage I NSCLC indicates a poor prognosis. Retinoids have been shown to prevent induction of COX-2 by mitogens and tumor promoters. Expression of COX-2 correlated with RAR-β expression (P = 0.053), but not with k-ras mutational status, vascular endothelial growth factor, basic fibroblast growth factor, interleukin 8 levels, or other markers of angiogenesis, invasion, and metastases. Thus, like RAR-β positivity, COX-2 overexpression appears to portend a shorter survival among patients with early stage non-small cell lung cancer. Future studies of RAR-β and COX-2 regulation in NSCLC should further the development of prevention and therapy interventions with retinoids and/or COX-2 antagonists in this patient population.