Showing papers by "University of Alabama at Birmingham published in 2002"
TL;DR: Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated, while new-onset diabetes was less frequent with losartan.
5,380 citations
TL;DR: Representatives from many countries serve as a network for the dissemination and implementation of programs for diagnosis, management, and prevention of COPD.
Abstract: Representatives from many countries serve as a network for the dissemination and implementation of programs for diagnosis, management, and prevention of COPD. The GOLD Board of Directors is grateful to the many GOLD National Leaders who participated in discussions of concepts that appear in GOLD reports.
3,165 citations
Emory University1, Research Triangle Park2, Case Western Reserve University3, National Institutes of Health4, University of Alabama at Birmingham5, Yale University6, Indiana University7, University of Cincinnati8, Boston Children's Hospital9, University of Texas Health Science Center at Houston10, Brown University11, University of Miami12, University of Tennessee Health Science Center13, Wayne State University14, University of Texas Southwestern Medical Center15, Stanford University16, University of New Mexico17
TL;DR: Infants who developed late-onset sepsis had a significantly prolonged hospital stay and were significantly more likely to die than those who were uninfected, especially if they were infected with Gram-negative organisms or fungi.
Abstract: Objective. Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 6956 VLBW (401–1500 g) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period (1998–2000). Methods. The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospective registry of all VLBW neonates admitted to participating centers within 14 days of birth. Expanded infection surveillance was added in 1998. Results. Of 6215 infants who survived beyond 3 days, 1313 (21%) had 1 or more episodes of blood culture-proven late-onset sepsis. The vast majority of infections (70%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 48% of infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus, prolonged ventilation, prolonged intravascular access, bronchopulmonary dysplasia, and necrotizing enterocolitis. Infants who developed late-onset sepsis had a significantly prolonged hospital stay (mean length of stay: 79 vs 60 days). They were significantly more likely to die than those who were uninfected (18% vs 7%), especially if they were infected with Gram-negative organisms (36%) or fungi (32%). Conclusions. Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors. Strategies to reduce late-onset sepsis and its medical, social, and economic toll need to be addressed urgently.
2,102 citations
University of Texas Southwestern Medical Center1, University of Michigan2, University of Washington3, University of California, San Francisco4, University of California, Los Angeles5, University of Nebraska Omaha6, University of Pittsburgh7, Mayo Clinic8, Baylor University Medical Center9, Northwestern University10, Washington University in St. Louis11, Icahn School of Medicine at Mount Sinai12, Oregon Health & Science University13, University of Miami14, Yale University15, University of Alabama at Birmingham16, Harvard University17
TL;DR: The primary aim was to compare presenting clinical features and liver transplantation in patients with acute liver failure related to acetaminophen hepatotoxicity, other drugs, indeterminate factors, and other causes.
Abstract: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent causes of acute liver failure. The cause of liver failure and coma grade at admission were...
1,988 citations
TL;DR: Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities and were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals.
Abstract: ContextCognitive function in older adults is related to independent living
and need for care. However, few studies have addressed whether improving cognitive
functions might have short- or long-term effects on activities related to
living independently.ObjectiveTo evaluate whether 3 cognitive training interventions improve mental
abilities and daily functioning in older, independent-living adults.DesignRandomized, controlled, single-blind trial with recruitment conducted
from March 1998 to October 1999 and 2-year follow-up through December 2001.Setting and ParticipantsVolunteer sample of 2832 persons aged 65 to 94 years recruited from
senior housing, community centers, and hospital/clinics in 6 metropolitan
areas in the United States.InterventionsParticipants were randomly assigned to 1 of 4 groups: 10-session group
training for memory (verbal episodic memory; n = 711), or reasoning (ability
to solve problems that follow a serial pattern; n = 705), or speed of processing
(visual search and identification; n = 712); or a no-contact control group
(n = 704). For the 3 treatment groups, 4-session booster training was offered
to a 60% random sample 11 months later.Main Outcome MeasuresCognitive function and cognitively demanding everyday functioning.ResultsThirty participants were incorrectly randomized and were excluded from
the analysis. Each intervention improved the targeted cognitive ability compared
with baseline, durable to 2 years (P<.001 for
all). Eighty-seven percent of speed-, 74% of reasoning-, and 26% of memory-trained
participants demonstrated reliable cognitive improvement immediately after
the intervention period. Booster training enhanced training gains in speed
(P<.001) and reasoning (P<.001)
interventions (speed booster, 92%; no booster, 68%; reasoning booster, 72%;
no booster, 49%), which were maintained at 2-year follow-up (P<.001 for both). No training effects on everyday functioning were
detected at 2 years.ConclusionsResults support the effectiveness and durability of the cognitive training
interventions in improving targeted cognitive abilities. Training effects
were of a magnitude equivalent to the amount of decline expected in elderly
persons without dementia over 7- to 14-year intervals. Because of minimal
functional decline across all groups, longer follow-up is likely required
to observe training effects on everyday function.
1,878 citations
TL;DR: Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes, and LVH.
1,558 citations
TL;DR: These findings provide the first evidence for the rapid emergence of clinical resistance to a novel class of HIV-1 entry inhibitors and may be relevant to future treatment strategies involving these agents.
Abstract: The synthetic peptide T-20 (enfuvirtide) represents the first of a new class of antiretroviral compounds to demonstrate in vivo potency by targeting a step in viral entry. T-20 inhibits a conformational change in the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein (gp41) that is required for fusion between HIV-1 and target cell membranes. The initial phase I clinical trial of T-20 treatment for HIV-infected patients thus provided a unique opportunity to evaluate the emergence of resistant virus in vivo to this novel class of antiretroviral agents. All four patients who received an intermediate dose of T-20 (30 mg twice daily) had an initial decline in plasma viral load over the first 10 days but a rising trend by day 14, suggestive of selection for resistant virus. Plasma virus derived from patients enrolled in all dosage groups of the phase I T-20 trial was analyzed by population sequencing before and after treatment. While no mutations were found within a highly conserved 3-amino-acid sequence (GIV) known to be critical for fusion at baseline, after 14 days of therapy, virus from one patient in the 30-mg dose group (30-1) developed a mutation in this motif, specifically an aspartic acid (D) substitution for glycine (G) at position 36. Multiple env clones were derived from the plasma virus of all four patients in the 30-mg dosage group. Sequence analysis of 49 clones derived from the plasma of patient 30-1 on day 14 revealed that 25 clones contained the G36D mutation, while 8 contained the V38A mutation. Dual mutations involving G36D and other residues within the HR1 domain were also identified. In 5 of the 49 env clones, other mutations involving residues 32 (Q32R or Q32H) and 39 (Q39R) were found in combination with G36D. Cloned env sequences derived from the plasma virus of subject 30-3 also had single mutations in the GIV sequence (V38M and I37V) detectable following therapy with T-20. The plasma virus from subjects 30-2 and 30-4 did not contain changes within the GIV sequence. To analyze the biological resistance properties of these mutations, we developed a novel single-cycle HIV-1 entry assay using JC53BL cells which express beta-galactosidase and luciferase under control of the HIV-1 long terminal repeat. Full-length env clones were derived from the plasma virus of patients 30-1 and 30-3 and used to generate pseudotyped virus stocks. The mean 50% inhibition concentrations (IC(50)s) for mutants G36D and V38A (patient 30-1) were 2.3 microg/ml and 11.2 microg/ml, respectively, statistically significant increases of 9.1- and 45-fold, respectively, compared with those of wild-type Env. The IC(50) for the V38 M mutation (patient 30-3) was 7.6 microg/ml, an 8-fold increase compared with that of the wild type. The I37V mutation resulted in an IC(50) 3.2-fold greater than that of the wild type. Envs with double mutations (Q32R plus G36D and Q32H plus G36D) exhibited a level of resistance similar to that of G36D alone. These findings provide the first evidence for the rapid emergence of clinical resistance to a novel class of HIV-1 entry inhibitors and may be relevant to future treatment strategies involving these agents.
1,542 citations
TL;DR: New guidelines for laboratory testing for patients with diabetes mellitus provide specific recommendations that are based on published data or derived from expert consensus, and several analytes have minimal clinical value at present and are not recommended.
Abstract: Background: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus The quality of the scientific evidence supporting the use of these assays varies substantially
Approach: An expert committee drafted evidence-based recommendations for the use of laboratory analysis in patients with diabetes An external panel of experts reviewed a draft of the guidelines, which were modified in response to the reviewers’ suggestions A revised draft was posted on the Internet and was presented at the AACC Annual Meeting in July, 2000 The recommendations were modified again in response to oral and written comments The guidelines were reviewed by the Professional Practice Committee of the American Diabetes Association
Content: Measurement of plasma glucose remains the sole diagnostic criterion for diabetes Monitoring of glycemic control is performed by the patients, who measure their own plasma or blood glucose with meters, and by laboratory analysis of glycated hemoglobin The potential roles of noninvasive glucose monitoring, genetic testing, autoantibodies, microalbumin, proinsulin, C-peptide, and other analytes are addressed
Summary: The guidelines provide specific recommendations based on published data or derived from expert consensus Several analytes are of minimal clinical value at the present time, and measurement of them is not recommended
1,481 citations
TL;DR: It is indicated that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women, irrespective of race or ethnic group, age, and body-mass index.
Abstract: Background The role of walking, as compared with vigorous exercise, in the prevention of cardiovascular disease remains controversial. Data for women who are members of minority racial or ethnic groups are particularly sparse. Methods We prospectively examined the total physical-activity score, walking, vigorous exercise, and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women's Health Initiative Observational Study. At base line, participants were free of diagnosed cardiovascular disease and cancer, and all participants completed detailed questionnaires about physical activity. We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events. Results An increasing physical-activity score had a strong, graded, inverse association with the risk of both coronary events and total cardiovascular events. There were similar findings among white women and bl...
1,352 citations
TL;DR: In this article, the authors evaluated the effect of intravenous milrinone on intermediate-term clinical outcomes of patients with chronic heart failure in a randomized, double-blind, placebo-controlled trial.
Abstract: Context Little randomized evidence is available to guide the in-hospital management of patients with an acute exacerbation of chronic heart failure. Although intravenous inotropic therapy usually produces beneficial hemodynamic effects and is labeled for use in the care of such patients, the effect of such therapy on intermediate-term clinical outcomes is uncertain. Objective To prospectively test whether a strategy that includes short-term use of milrinone in addition to standard therapy can improve clinical outcomes of patients hospitalized with an exacerbation of chronic heart failure. Design Prospective, randomized, double-blind, placebo-controlled trial conducted from July 1997 through November 1999. Setting Seventy-eight community and tertiary care hospitals in the United States. Participants A total of 951 patients admitted with an exacerbation of systolic heart failure not requiring intravenous inotropic support (mean age, 65 years; 92% with baseline New York Heart Association class III or IV; mean left ventricular ejection fraction, 23%). Intervention Patients were randomly assigned to receive a 48-hour infusion of either milrinone, 0.5 microg/kg per minute initially (n = 477), or saline placebo (n = 472). Main outcome measure Cumulative days of hospitalization for cardiovascular cause within 60 days following randomization. Results The median number of days hospitalized for cardiovascular causes within 60 days after randomization did not differ significantly between patients given milrinone (6 days) compared with placebo (7 days; P =.71). Sustained hypotension requiring intervention (10.7% vs 3.2%; P Conclusion These results do not support the routine use of intravenous milrinone as an adjunct to standard therapy in the treatment of patients hospitalized for an exacerbation of chronic heart failure.
1,086 citations
TL;DR: This review focuses on the specific roles of ROS and RNS in the cellular response to hypoxia and subsequent cytolytic injury during reoxygenation.
Abstract: Exacerbation of hypoxic injury after restoration of oxygenation (reoxygenation) is an important mechanism of cellular injury in transplantation and in myocardial, hepatic, intestinal, cerebral, ren...
National Institutes of Health1, University of Alabama at Birmingham2, University of California, Los Angeles3, Case Western Reserve University4, University of Utah5, New York Medical College6, Virginia Commonwealth University7, Loyola University Chicago8, University of Kentucky9, University of Virginia10, University of Pennsylvania11, Rowan University12, University of Florida13, Mayo Clinic14, Harvard University15, Université de Montréal16, Duke University17, University of Ottawa18, University of Arkansas at Little Rock19
TL;DR: Voriconazole is a suitable alternative to amphotericin B preparations for empirical antifungal therapy in patients with neutropenia and persistent fever in a randomized, international, multicenter trial.
Abstract: Background Patients with neutropenia and persistent fever are often treated empirically with amphotericin B or liposomal amphotericin B to prevent invasive fungal infections. Antifungal triazoles offer a potentially safer and effective alternative. Methods In a randomized, international, multicenter trial, we compared voriconazole, a new second-generation triazole, with liposomal amphotericin B for empirical antifungal therapy. Results A total of 837 patients (415 assigned to voriconazole and 422 to liposomal amphotericin B) were evaluated for success of treatment. The overall success rates were 26.0 percent with voriconazole and 30.6 percent with liposomal amphotericin B (95 percent confidence interval for the difference, –10.6 to 1.6 percentage points); these rates were independent of the administration of antifungal prophylaxis or the use of colony-stimulating factors. There were fewer documented breakthrough fungal infections in patients treated with voriconazole than in those treated with liposomal a...
TL;DR: Co-localization in cilia of polycystin-1 and polycyStin-2 is demonstrated, which is the principal proteins involved in autosomal dominant polycystic kidney disease, with polaris and cystin, which are proteins that are disrupted in the Tg737(orpk)and cpk mouse models of autosomal recessive polycysts disease, respectively.
Abstract: Recent evidence has suggested an association between structural and/or functional defects in the primary apical cilium of vertebrate epithelia and polycystic kidney disease (PKD). In Caenorhabditis elegans, the protein orthologues of the PKD-related proteins, polycystin-1 (LOV-1), polycystin-2 (PKD2), and polaris (OSM-5), co-localize in the cilia of male-specific sensory neurons, and defects in these proteins cause abnormalities of cilia structure and/or function. This study sought to determine whether the mammalian polycystins are expressed in primary cilia of renal epithelia and whether these proteins co-localize with polaris and cystin, the newly described, cilia-associated protein that is disrupted in the cpk mouse. To begin to address this issue, the expression of the protein products encoded by the PKD1, PKD2, Tg737, and cpk genes were examined in mouse cortical collecting duct (mCCD) cells using an immunofluorescence-based approach with a series of previously well-characterized antibodies. The mCCD cells were grown on cell culture inserts to optimize cell polarization and cilia formation. The data demonstrate co-localization in cilia of polycystin-1 and polycystin-2, which are the principal proteins involved in autosomal dominant polycystic kidney disease, with polaris and cystin, which are proteins that are disrupted in the Tg737(orpk)and cpk mouse models of autosomal recessive polycystic kidney disease, respectively. These data add to a growing body of evidence that suggests that primary cilium plays a key role in normal physiologic functions of renal epithelia and that defects in ciliary function contribute to the pathogenesis of PKD.
TL;DR: One of the subunits of the phagocyte NAD PH oxidase is now recognized as a member of a family of NADPH oxidases, or NOX, present in cells other than phagocytes, present at the plasma membrane from resident plasma membrane and cytosolic protein components.
Abstract: Phagocytes such as neutrophils and macrophages produce reactive oxygen species (ROS) during phagocytosis or stimulation with a wide variety of agents through activation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase that is assembled at the plasma membrane from resident plasma membrane and cytosolic protein components. One of the subunits of the phagocyte NADPH oxidase is now recognized as a member of a family of NADPH oxidases, or NOX, present in cells other than phagocytes. Physiologic generation of ROS has been implicated in a variety of physiologic responses from transcriptional activation to cell proliferation and apoptosis. The increase in superoxide and hydrogen peroxide (H2O2) that results from stimulation of the NADPH oxidase is transient, in part due to the presence of the antioxidant enzymes, which return their concentrations to the prestimulation steady state level. Thus, the antioxidant enzymes may function in the “turn-off” phase of signal transduction by ROS. During ...
TL;DR: Recent advances in genomics and proteomics, combined with the facilitated generation and analysis of transgenic and gene-knockout animals, have revealed new complexities in classical biological systems, including the B-cell compartment.
Abstract: Recent advances in genomics and proteomics, combined with the facilitated generation and analysis of transgenic and gene-knockout animals, have revealed new complexities in classical biological systems, including the B-cell compartment. Studies on an 'old', but poorly characterized, B-cell subset--the naive, marginal-zone (MZ) B-cell subset--over the past two years have spawned an avalanche of data that encompass the generation and function of these cells. Now that the initial 'infatuation' is over, it is time to reconsider these data and generate some conclusions that can be incorporated into a working model of the B-cell system.
TL;DR: It is the aim that this commentary will lead the reader to appreciate that studies investigating the signaling for and regulation of thiol metabolism must never be generalized, and that perturbations in any of step ofThioredoxin and glutathione metabolism may have etiological roles in genetically, virally, and environmentally borne pathologies.
TL;DR: Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity, arresting structural damage, and decreasing disability over 2 years in patients with early, aggressive RA.
Abstract: Objective
To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis (RA) who received monotherapy with either etanercept or methotrexate (MTX) for 2 years and to assess the safety of this therapy.
Methods
In the Enbrel ERA (early rheumatoid arthritis) trial, 632 patients with early, active RA were randomized to receive either twice-weekly subcutaneous etanercept (10 mg or 25 mg) or weekly oral MTX (mean dosage 19 mg per week) for at least 1 year in a double-blind manner. Following the blinded phase of the trial, 512 patients continued to receive the therapy to which they had been randomized for up to 1 additional year, in an open-label manner. Radiograph readers remained blinded to treatment group assignment and the chronologic order of images.
Results
At 24 months, more 25-mg etanercept patients than MTX patients met American College of Rheumatology 20% improvement criteria (72% and 59%, respectively; P = 0.005), and more had no increase in total score and erosion scores on the Sharp scale (P = 0.017 and P = 0.012, respectively). The mean changes in total Sharp score and erosion score in the 25-mg etanercept group (1.3 and 0.66 units, respectively) were significantly lower than those in the MTX group (3.2 and 1.86 units, respectively; P = 0.001). Significantly more patients in the 25-mg etanercept group (55%) than in the MTX group (37%) had at least 0.5 units of improvement in the Health Assessment Questionnaire disability index (P < 0.001). Fewer patients in the etanercept group than in the MTX group experienced adverse events or discontinued treatment because of adverse events.
Conclusion
Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity, arresting structural damage, and decreasing disability over 2 years in patients with early, aggressive RA.
TL;DR: Implementing these measures is likely to increase the prevalence of fistulas in any given dialysis unit, however, differences among dialysis units are likely to persist because of differences in gender, race, and co-morbidity mix of the patient population.
TL;DR: Caspase-8 deficiency in humans is compatible with normal development and shows that caspases has a postnatal role in immune activation of naive lymphocytes, which leads to immunodeficiency.
Abstract: Apoptosis is a form of programmed cell death that is controlled by aspartate-specific cysteine proteases called caspases. In the immune system, apoptosis counters the proliferation of lymphocytes to achieve a homeostatic balance, which allows potent responses to pathogens but avoids autoimmunity. The CD95 (Fas, Apo-1) receptor triggers lymphocyte apoptosis by recruiting Fas-associated death domain (FADD), caspase-8 and caspase-10 proteins into a death-inducing signalling complex. Heterozygous mutations in CD95, CD95 ligand or caspase-10 underlie most cases of autoimmune lymphoproliferative syndrome (ALPS), a human disorder that is characterized by defective lymphocyte apoptosis, lymphadenopathy, splenomegaly and autoimmunity. Mutations in caspase-8 have not been described in ALPS, and homozygous caspase-8 deficiency causes embryonic lethality in mice. Here we describe a human kindred with an inherited genetic deficiency of caspase-8. Homozygous individuals manifest defective lymphocyte apoptosis and homeostasis but, unlike individuals affected with ALPS, also have defects in their activation of T lymphocytes, B lymphocytes and natural killer cells, which leads to immunodeficiency. Thus, caspase-8 deficiency in humans is compatible with normal development and shows that caspase-8 has a postnatal role in immune activation of naive lymphocytes.
TL;DR: Recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory are reviewed.
Abstract: One of the most rigorously investigated problems in modern neuroscience is to decipher the mechanisms by which experience-induced changes in the central nervous system are translated into behavioral acquisition, consolidation, retention, and subsequent recall of information. Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Recent experimental evidence indicates that BDNF modulates synaptic transmission and plasticity by acting across different spatial and temporal domains. BDNF signaling evokes both short- and long-term periods of enhanced synaptic physiology in both pre- and postsynaptic compartments of central synapses. Specifically, BDNF/TrkB signaling converges on the MAP kinase pathway to enhance excitatory synaptic transmission in vivo, as well as hippocampal-dependent learning in behaving animals. Emerging concepts of the intracellular signaling cascades involved in synaptic plasticity induced through environmental interactions resulting in behavioral learning further support the contention that BDNF/TrkB signaling plays a fundamental role in mediating enduring changes in central synaptic structure and function. Here we review recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory.
TL;DR: Myeloperoxidase, an abundant mammalian phagocyte hemoprotein thought to primarily mediate host defense reactions, can directly modulate vascular inflammatory responses by regulating NO bioavailability during acute inflammation.
Abstract: Myeloperoxidase (MPO) is an abundant mammalian phagocyte hemoprotein thought to primarily mediate host defense reactions. Although its microbicidal functions are well established in vitro, humans deficient in MPO are not at unusual risk of infection. MPO was observed herein to modulate the vascular signaling and vasodilatory functions of nitric oxide (NO) during acute inflammation. After leukocyte degranulation, MPO localized in and around vascular endothelial cells in a rodent model of acute endotoxemia and impaired endothelium-dependent relaxant responses, to which MPO-deficient mice were resistant. Altered vascular responsiveness was due to catalytic consumption of NO by substrate radicals generated by MPO. Thus MPO can directly modulate vascular inflammatory responses by regulating NO bioavailability.
TL;DR: The data provide strong evidence that hyperaldosteronism is a common cause of resistant hypertension in black and white subjects and the accuracy of these results is strengthened by having done suppression testing of all evaluated subjects.
Abstract: Recent reports suggesting that the prevalence of primary hyperaldosteronism may be higher than historically thought have relied on an elevated plasma aldosterone concentration/plasma renin activity ratio to either diagnose or identify subjects at high risk of having primary hyperaldosteronism and have not included suppression testing of all evaluated subjects. In this prospective study of 88 consecutive patients referred to a university clinic for resistant hypertension, we determined the 24-hour urinary aldosterone excretion during high dietary salt ingestion, baseline plasma renin activity, and plasma aldosterone in all subjects. Primary hyperaldosteronism was confirmed if plasma renin activity was 12 microg/24-hour during high urinary sodium excretion (>200 mEq/24-hour). Eighteen subjects (20%) were confirmed to have primary hyperaldosteronism. The prevalence of hyperaldosteronism was similar in black and white subjects. Of the 14 subjects with confirmed hyperaldosteronism who have been treated with spironolactone, all have manifested a significant reduction in blood pressure. In this population, an elevated plasma aldosterone/plasma renin activity ratio (>20) had a sensitivity of 89% and a specificity of 71% with a corresponding positive predictive value of 44% and a negative predictive value of 96%. These data provide strong evidence that hyperaldosteronism is a common cause of resistant hypertension in black and white subjects. The accuracy of these results is strengthened by having done suppression testing of all evaluated subjects.
TL;DR: It is shown that blood-derived neutrophil granulocytes and CD11c(lo) immature dendritic cells (DC) are the primary cells that efficiently capture and transport particulate bacteria to the spleen.
TL;DR: Studies of phenomena such as cortical reorganization after a lesion, central nervous system repair, and the substantial enhancement of extremity use and linguistic function by behavioural therapy, support this emerging view.
Abstract: Recent discoveries about how the central nervous system responds to injury and how patients reacquire lost behaviours by training have yielded promising new therapies for neurorehabilitation. Until recently, this field had been largely static, but the current melding of basic behavioural science with neuroscience promises entirely new approaches to improving behavioural, perceptual and cognitive capabilities after neurological damage. Studies of phenomena such as cortical reorganization after a lesion, central nervous system repair, and the substantial enhancement of extremity use and linguistic function by behavioural therapy, support this emerging view. The ongoing changes in rehabilitation strategies might well amount to an impending paradigm shift in this field.
TL;DR: In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone.
Abstract: Objective
To evaluate the efficacy and safety of anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA).
Methods
Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for ≥3 months (those with disease duration of >6 months but <12 years) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12.
Results
A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0-mg/kg (46%; P = 0.001) and 2.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% (2.0-mg/kg group) of patients receiving higher doses.
Conclusion
In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone.
TL;DR: This review discusses the demographics, etiology, clinical presentation, laboratory evaluation, and treatment options of autoimmune hemolytic anemia, which includes warm AIHA, cold agglutinin syndrome, paroxysmal cold hemoglobinuria, mixed‐type AIH, and drug‐induced AIHA.
Abstract: Red blood cell (RBC) autoantibodies are a relatively uncommon cause of anemia. However, autoimmune hemolytic anemia (AIHA) must be considered in the differential diagnosis of hemolytic anemias, especially if the patient has a concomitant lymphoproliferative disorder, autoimmune disease, or viral or mycoplasmal infection. Classifications of AIHA include warm AIHA, cold agglutinin syndrome, paroxysmal cold hemoglobinuria, mixed-type AIHA, and drug-induced AIHA. Characteristics of the autoantibodies are responsible for the various clinical entities. As a result, diagnosis is based on the clinical presentation and a serologic work-up. For each classification of AIHA, this review discusses the demographics, etiology, clinical presentation, laboratory evaluation, and treatment options.
TL;DR: This work applies laser–Raman spectroscopic imagery of individual microscopic fossils to exceptionally ancient fossil microbe-like objects, including the oldest such specimens reported from the geological record, and shows that the results obtained substantiate the biological origin of the earliest cellular fossils known.
Abstract: Unlike the familiar Phanerozoic history of life, evolution during the earlier and much longer Precambrian segment of geological time centred on prokaryotic microbes1. Because such microorganisms are minute, are preserved incompletely in geological materials, and have simple morphologies that can be mimicked by nonbiological mineral microstructures, discriminating between true microbial fossils and microscopic pseudofossil ‘lookalikes’ can be difficult2,3. Thus, valid identification of fossil microbes, which is essential to understanding the prokaryote-dominated, Precambrian 85% of life's history, can require more than traditional palaeontology that is focused on morphology. By combining optically discernible morphology with analyses of chemical composition, laser–Raman spectroscopic imagery of individual microscopic fossils provides a means by which to address this need. Here we apply this technique to exceptionally ancient fossil microbe-like objects, including the oldest such specimens reported from the geological record, and show that the results obtained substantiate the biological origin of the earliest cellular fossils known.
University of California, San Francisco1, Stanford University2, George Washington University3, Memorial Hospital of South Bend4, Duke University5, University of Alabama at Birmingham6, Johns Hopkins University7, Hartford Hospital8, Université de Montréal9, University of Ottawa10, University of Minnesota11, National Institutes of Health12
TL;DR: In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit and a potential for harm was suggested with each treatment.
Abstract: ContextHormone replacement therapy (HRT) and antioxidant vitamins are widely
used for secondary prevention in postmenopausal women with coronary disease,
but no clinical trials have demonstrated benefit to support their use.ObjectiveTo determine whether HRT or antioxidant vitamin supplements, alone or
in combination, influence the progression of coronary artery disease in postmenopausal
women, as measured by serial quantitative coronary angiography.Design, Setting, and PatientsThe Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized,
double-blind trial of 423 postmenopausal women with at least one 15% to 75%
coronary stenosis at baseline coronary angiography. The trial was conducted
from July 1997 to January 2002 in 7 clinical centers in the United States
and Canada.InterventionsPatients were randomly assigned in a 2 × 2 factorial design to
receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of
medroxyprogesterone acetate for women who had not had a hysterectomy), or
matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin
C twice daily, or placebo.Main Outcome MeasureAnnualized mean (SD) change in minimum lumen diameter (MLD) from baseline
to concluding angiogram of all qualifying coronary lesions averaged for each
patient. Patients with intercurrent death or myocardial infarction (MI) were
imputed the worst rank of angiographic outcome.ResultsThe mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary
progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15)
mm/y and by 0.024 (0.15) mm/y with HRT placebo (P =
.17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo
by 0.028 (0.15) mm/y (P = .32). When patients with
intercurrent death or MI were included, the primary outcome showed an increased
risk for women in the active HRT group (P = .045),
and suggested an increased risk in the active vitamin group (P = .09). Fourteen patients died in the HRT group and 8 in the HRT
placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3),
and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95%
CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs
15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and
18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction
between the 2 treatment interventions.ConclusionIn postmenopausal women with coronary disease, neither HRT nor antioxidant
vitamin supplements provide cardiovascular benefit. Instead, a potential for
harm was suggested with each treatment.
TL;DR: In this article, the functional outcome of a serious eye injury can be predicted with reasonable certainty based on a standardized terminology of ocular trauma terms, and using a very large number of injuries treated by a wide variety of ophthalmologists.
Abstract: Only based on a standardized terminology of ocular trauma terms, and using a very large number of injuries treated by a wide variety of ophthalmologists, could a reliable method be developed so that the functional outcome of a serious eye injury can be predicted with reasonable certainty. The authors used the databases of the United States and Hungarian Eye Injury Registries and, with a grant from the National Center for Injury Prevention at the Centers for Disease Control and Prevention, designed such a system.