Showing papers by "University of Texas Health Science Center at Houston published in 2003"

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Abstract: Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

The VIVA Trial Vascular Endothelial Growth Factor in Ischemia for Vascular Angiogenesis

Abstract: Background— Recombinant human vascular endothelial growth factor protein (rhVEGF) stimulates angiogenesis in animal models and was well tolerated in Phase I clinical trials. VIVA (Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis) is a double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of intracoronary and intravenous infusions of rhVEGF. Methods and Results— A total of 178 patients with stable exertional angina, unsuitable for standard revascularization, were randomized to receive placebo, low-dose rhVEGF (17 ng · kg−1 · min−1), or high-dose rhVEGF (50 ng · kg−1 · min−1) by intracoronary infusion on day 0, followed by intravenous infusions on days 3, 6, and 9. Exercise treadmill tests, angina class, and quality of life assessments were performed at baseline, day 60, and day 120. Myocardial perfusion imaging was performed at baseline and day 60. At day 60, the change in exercise treadmill test (ETT) time from baseline was not different between groups...

Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population

Abstract: Objective To estimate the prevalence, incidence, survival, and disease characteristics of systemic sclerosis (SSc) in the Detroit tricounty area. Methods A census of SSc cases for the period 1989–1991 was conducted in the Detroit area, using multiple sources for case identification. Diagnoses were verified by medical record review. Capture-recapture analysis was used to estimate the total SSc population. Cases of localized scleroderma (morphea and linear disease) were excluded. Results Based on 706 verified cases of SSc, prevalence was initially estimated to be 242.0 cases per million adults (95% confidence interval [95% CI] 213–274), with an annual incidence of 19.3 new cases per million adults per year (95% CI 12.4–30.2). Capture-recapture analysis, based on the degree of overlap of verified cases among multiple sources, resulted in a revised prevalence estimate of 276 cases per million adults (95% CI 245–310). Sex- and race-specific prevalence estimates were significantly higher for women than for men, and for blacks than for whites. The average age at diagnosis was significantly younger for blacks than for whites. Compared with white patients, black patients were almost twice as likely to have diffuse disease (prevalence proportion ratio 1.86, 95% CI 1.48–2.35). Median survival was ∼11 years. Factors negatively affecting survival included male sex (hazard ratio 1.81, 95% CI 1.29–2.55) and older age at diagnosis (hazard ratio 1.04, 95% CI 1.03–1.05). Conclusion This study establishes baseline estimates of SSc occurrence and characteristics in a large US cohort consisting primarily of black adults and white adults. These data should facilitate research regarding the role of geographic, ethnic, racial, and environmental factors for this disease in comparison populations.

The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria

Abstract: Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis.

A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients.

Abstract: We conducted a prospective, multicenter observational study of adults (n=1447) and children (n=144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P<.001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P<.001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials.

Discrepant attitudes about teamwork among critical care nurses and physicians.

Abstract: ObjectiveTo measure and compare critical care physicians’ and nurses’ attitudes about teamwork.DesignCross-sectional surveys.SettingEight nonsurgical intensive care units in two teaching and four nonteaching hospitals in the Houston, TX, metropolitan area.SubjectsPhysicians and nurses who worked in

The versatile bacterial type iv secretion systems

Abstract: Bacteria use type IV secretion systems for two fundamental objectives related to pathogenesis — genetic exchange and the delivery of effector molecules to eukaryotic target cells. Whereas gene acquisition is an important adaptive mechanism that enables pathogens to cope with a changing environment during invasion of the host, interactions between effector and host molecules can suppress defence mechanisms, facilitate intracellular growth and even induce the synthesis of nutrients that are beneficial to bacterial colonization. Rapid progress has been made towards defining the structures and functions of type IV secretion machines, identifying the effector molecules, and elucidating the mechanisms by which the translocated effectors subvert eukaryotic cellular processes during infection.

Prospective association between obesity and depression: evidence from the Alameda County Study.

Abstract: OBJECTIVE: To examine the temporal relation between obesity and depression to determine if each constitutes a risk factor for the other. DESIGN: A two-wave, 5-y-observational study with all measures at both times. SUBJECTS: A total of 2123 subjects, 50 y of age and older, who participated in the 1994 and 1999 waves of the Alameda County Study. MEASUREMENTS: Obesity defined as body mass index (BMI)⩽30. Depression assessed using DSM-IV symptom criteria for major depressive episodes. Covariates include indicators of age, gender, education, marital status, social support, life events, physical health problems, and functional limitations. RESULTS: Obesity at baseline was associated with increased risk of depression 5 y later, even after controlling for depression at baseline and an array of covariates. The reverse was not true; depression did not increase the risk of future obesity. CONCLUSION: These results, the first ever on reciprocal effects between obesity and depression, add to a growing body of evidence concerning the adverse effects of obesity on mental health. More studies are needed on the relation between obesity and mental health and implications for prevention and treatment.

Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome

Abstract: Antiphospholipid syndrome (APS) is defined by recurrent pregnancy loss and thrombosis in the presence of antiphospholipid (aPL) Ab’s. Currently, therapy for pregnant women with APS is focused on preventing thrombosis, but anticoagulation is only partially successful in averting miscarriage. We hypothesized that complement activation is a central mechanism of pregnancy loss in APS and tested this in a model in which pregnant mice receive human IgG containing aPL Ab’s. Here we identify complement component C5 (and particularly its cleavage product C5a) and neutrophils as key mediators of fetal injury, and we show that Ab’s or peptides that block C5a–C5a receptor interactions prevent pregnancy complications. The fact that F(ab)′2 fragments of aPL Ab’s do not mediate fetal injury and that C4-deficient mice are protected from fetal injury suggests that activation of the complement cascade is initiated via the classical pathway. Studies in factor B–deficient mice, however, indicate that alternative pathway activation is required and amplifies complement activation. In contrast, activating FcγRs do not play an important role in mediating aPL Ab–induced fetal injury. Our findings identify the key innate immune effectors engaged by pathogenic autoantibodies that mediate poor pregnancy outcomes in APS and provide novel and important targets for prevention of pregnancy loss in APS.

National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification.

Abstract: Objectives. A series of new guidelines has been developed by the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative to improve the detection and management of chronic kidney disease (CKD). In most instances of CKD, the earliest manifestations of the disorder may be identified by relatively simple tests. Unfortunately, CKD is often “underdiagnosed,” in part because of the absence of a common definition of CKD and a classification of the stages in its progression. The Kidney Disease Outcomes Quality Initiative clinical practice guidelines for CKD evaluation, classification, and stratification provide a basis to remedy these deficits. The specific goals of the guidelines described in this review are to provide: 1) an overview of the clinical practice guidelines as they pertain to children and adolescents, 2) a simple classification of the stages of CKD, and 3) a practical approach to the laboratory assessment of kidney disease in children and adolescents. Methods. The guidelines were developed as part of an evidence-based evaluation of CKD and its consequences in patients of all ages. The data that were used to generate the guidelines in this article were extracted from a structured analysis of articles that reported on children with CKD. Results and Conclusions. This review presents the definition and 5-stage classification system of CKD developed by the work group assigned to develop the guidelines, and summarizes the major recommendations regarding the early detection of CKD. Major emphasis is placed on the identification of children and adolescents with CKD by measuring the protein-to-creatinine ratio in spot urine specimens and by estimating the glomerular filtration rate from serum creatinine using prediction equations.

Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients

Abstract: Object The current North American experience with minimally invasive vertebro- and kyphoplasty is largely limited to the treatment of benign osteoporotic compression fractures. The objective of this study was to assess the safety and efficacy of these procedures for painful vertebral body (VB) fractures in cancer patients. Methods The authors reviewed a consecutive group of cancer patients (21 with myeloma and 35 with other primary malignancies) undergoing vertebro- and kyphoplasty at their institution. Ninety-seven (65 vertebro- and 32 kyphoplasty) procedures were performed in 56 patients during 58 treatment sessions. The mean patient age was 62 years (+/- 13 years [standard deviation]) and the median duration of symptoms was 3.2 months. All patients suffered intractable spinal pain secondary to VB fractures. Patients noted marked or complete pain relief after 49 procedures (84%), and no change after five procedures (9%); early postoperative Visual Analog Scale (VAS) pain scores were unavailable in four patients (7%). No patient was worse after treatment. Reductions in VAS pain scores remained significant up to 1 year (p = 0.02, Wilcoxon signed-rank test). Analgesic consumption was reduced at 1 month (p = 0.03, Wilcoxon signed-rank test). Median follow-up length was 4.5 months (range 1 day-19.7 months). Asymptomatic cement leakage occurred during vertebroplasty at six (9.2%) of 65 levels; no cement extravasation was seen during kyphoplasty. There were no deaths or complications related to the procedures. The mean percentage of restored VB height by kyphoplasty was 42 +/- 21%. Conclusions Percutaneous vertebro- and kyphoplasty provided significant pain relief in a high percentage of patients, and this appeared durable over time. The absence of cement leakage-related complications may reflect the use of 1) high-viscosity cement; 2) kyphoplasty in selected cases; and 3) relatively small volume injection. Precise indications for these techniques are evolving; however, they are safe and feasible in well-selected patients with refractory spinal pain due to myeloma bone disease or metastases.

Novel Effects of Nitric Oxide

Abstract: Nitric oxide (NO), a simple free radical gas, elicits a surprisingly wide range of physiological and pathophysiological effects. NO interacts with soluble guanylate cyclase to evoke many of these effects. However, NO can also interact with molecular oxygen and superoxide radicals to produce reactive nitrogen species that can modify a number of macromolecules including proteins, lipids, and nucleic acids. NO can also interact directly with transition metals. Here, we have reviewed the non--3',5'-cyclic-guanosine-monophosphate-mediated effects of NO including modifications of proteins, lipids, and nucleic acids.

Antifungal Susceptibility Survey of 2,000 Bloodstream Candida Isolates in the United States

Abstract: Candida bloodstream isolates (n = 2,000) from two multicenter clinical trials carried out by the National Institute of Allergy and Infectious Diseases Mycoses Study Group between 1995 and 1999 were tested against amphotericin B (AMB), flucytosine (5FC), fluconazole (FLU), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), caspofungin (CFG), micafungin (MFG), and anidulafungin (AFG) using the NCCLS M27-A2 microdilution method. All drugs were tested in the NCCLS-specified RPMI 1640 medium except for AMB, which was tested in antibiotic medium 3. A sample of isolates was also tested in RPMI 1640 supplemented to 2% glucose and by using the diluent polyethylene glycol (PEG) in lieu of dimethyl sulfoxide for those drugs insoluble in water. Glucose supplementation tended to elevate the MIC, whereas using PEG tended to decrease the MIC. Trailing growth occurred frequently with azoles. Isolates were generally susceptible to AMB, 5FC, and FLU. Rates of resistance to ITR approached 20%. Although no established interpretative breakpoints are available for the candins (CFG, MFG, and AFG) and the new azoles (VOR and POS), they all exhibited excellent antifungal activity, even for those strains resistant to the other aforementioned agents.

Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome.

Abstract: Hypothesis Normal resuscitation (oxygen delivery index [DO 2 I] ≥500 mL/min per square meter), compared with supranormal trauma resuscitation (DO 2 I ≥600 mL/min per square meter), requires less crystalloid volume, thus decreasing the incidence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). Design Retrospective analysis of a prospective database. Setting Twenty-bed intensive care unit (ICU) in a regional level I trauma center. Patients Patients with major trauma (injury severity score >15, initial base deficit ≥6 mEq/L, or need for ≥6 units of packed red blood cells in the first 12 hours) or age 65 years or older with any 2 of the previous criteria. Interventions Shock/trauma resuscitation protocol: pulmonary artery catheter, gastric tonometry, urinary bladder pressure measurements, lactated Ringer infusion, packed red blood cell transfusion, and moderate inotrope support, as needed, in that sequence, to attain and maintain a DO 2 I greater than or equal to 600 mL/min per m 2 (16 months, ending January 1, 2001, n = 85) or a DO 2 I greater than or equal to 500 mL/min per square meter (16 months, starting January 1, 2001, n = 71) for the first 24 hours in the ICU. Main Outcome Measures: Lactated Ringer infusion volume (liters) at ICU admission, gastric partial carbon dioxide minus end-tidal carbon dioxide(GAP CO2 ), IAH (urinary bladder pressure measurements >20 mm Hg), ACS (urinary bladder pressure measurements >25 mm Hg with organ dysfunction), multiple organ failure, and mortality. Results Demographics, injury severity, and shock severity parameters were similar in both groups. The supranormal resuscitation group required more lactated Ringer infusion volume in the first 24 hours in the ICU (mean ± SD, 13 ± 2 vs 7 ± 1 L; P CO2 (16 ± 2 vs 7 ± 1 mm Hg; P P P P P Conclusion Supranormal resuscitation, compared with normal resuscitation, was associated with more lactated Ringer infusion, decreased intestinal perfusion (higher GAP CO2 ), and an increased incidence of IAH, ACS, multiple organ failure, and death.

Transdifferentiation of Human Peripheral Blood CD34+-Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo

Abstract: Background— Adult human peripheral blood cells have been shown to differentiate into mature cells of nonhematopoietic tissues, such as hepatocytes and epithelial cells of the skin and gastrointestinal track. We investigated whether these cells could also transdifferentiate into human cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo. Methods and Results— Myocardial infarction was created in SCID mice by occluding the left anterior descending coronary artery, after which adult peripheral blood CD34+ cells were injected into the tail vein. Hearts were harvested 2 months after injection and stained for human leukocyte antigen (HLA) and markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Cardiomyocytes, endothelial cells, and smooth muscle cells that bear HLA were identified in the infarct and peri-infarct regions of the mouse hearts. In a separate experiment, CD34+ cells were injected intraventricularly into mice without experimental myocardial infarction. HLA-posi...

Measuring errors and adverse events in health care

Abstract: In this paper, we identify 8 methods used to measure errors and adverse events in health care and discuss their strengths and weaknesses. We focus on the reliability and validity of each, as well as the ability to detect latent errors (or system errors) versus active errors and adverse events. We propose a general framework to help health care providers, researchers, and administrators choose the most appropriate methods to meet their patient safety measurement goals.

Coming of Age of C-Reactive Protein Using Inflammation Markers in Cardiology

Abstract: In a recently published prospective study comprising 28 000 women, Ridker et al1 showed that C-reactive protein (CRP) is a better predictor of the risk of cardiovascular events than low-density lipoprotein (LDL) cholesterol. The implication of this and many other supporting studies is profound and will change the way we screen and manage our patients with atherosclerosis and its associated clinical syndromes. CRP is one of the acute phase proteins that increase during systemic inflammation.2,3 Individuals without inflammation usually have CRP levels below 1 μg/mL; however, patients with bacterial infections, autoimmune diseases, and cancer frequently have CRP level as high as 100 μg/mL or even higher. It is clear that a high CRP level has no specificity in differentiating disease entities from one another. Despite its lack of specificity, CRP has now emerged as one of the most powerful predictors of cardiovascular risk. Even more remarkable, CRP’s predictive power resides in the range between 1 to 5 μg/mL, which was previously regarded to be normal in the era preceding the high-sensitivity CRP test. In fact, tests showing serum CRP levels greater than 10 μg/mL in apparently healthy men or women should be repeated to exclude occult infection or other systemic inflammatory process (see Figure). To understand CRP’s transition from an acute phase protein to a most useful inflammatory biomarker for predicting future cardiovascular events, we must know more about the role of the immune system in the pathogenesis of atherosclerosis. CRP level and cardiovascular risk. CRP levels are listed on the left and interpretations are on the …

14-3-3ε is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller–Dieker syndrome

Abstract: Heterozygous deletions of 17p13.3 result in the human neuronal migration disorders isolated lissencephaly sequence (ILS) and the more severe Miller–Dieker syndrome (MDS). Mutations in PAFAH1B1 (the gene encoding LIS1) are responsible for ILS and contribute to MDS, but the genetic causes of the greater severity of MDS are unknown. Here, we show that the gene encoding 14-3-3e (YWHAE), one of a family of ubiquitous phosphoserine/threonine–binding proteins, is always deleted in individuals with MDS. Mice deficient in Ywhae have defects in brain development and neuronal migration, similar to defects observed in mice heterozygous with respect to Pafah1b1. Mice heterozygous with respect to both genes have more severe migration defects than single heterozygotes. 14-3-3e binds to CDK5/p35-phosphorylated NUDEL and this binding maintains NUDEL phosphorylation. Similar to LIS1, deficiency of 14-3-3e results in mislocalization of NUDEL and LIS1, consistent with reduction of cytoplasmic dynein function. These results establish a crucial role for 14-3-3e in neuronal development by sustaining the effects of CDK5 phosphorylation and provide a molecular explanation for the differences in severity of human neuronal migration defects with 17p13.3 deletions.

Both primary and secondary abdominal compartment syndrome can be predicted early and are harbingers of multiple organ failure.

Abstract: Background: Primary (1°) abdominal compartment syndrome (ACS) is a known complication of damage control. Recently secondary (2°) ACS has been reported in patients without abdominal injury who require aggressive resuscitation. The purpose of this study was to compare the epidemiology of 1° and 2° ACS and develop early prediction models in a high-risk cohort who were treated in a similar fashion. Methods: Major torso trauma patients underwent standardized resuscitation and had prospective data collected including occurrence of ACS, demographics, ISS, urinary bladder pressure, gastric tonometry (GAP CO2 = gastric regional CO 2 minus end tidal CO 2 ), laboratory, respiratory, and hemodynamic data. With 1° and 2° ACS as endpoints, variables were tested by uni- and multivariate logistic analysis (MLA). Results: From 188 study patients during the 44-month period, 26 (14%) developed ACS-11 (6%) were 1° ACS and IS (8%) 2° ACS. 1° and 2° ACS had similar demographics, shock, and injury severity. Significant univariate differences included: time to decompression from ICU admit (600 ± 112 vs. 360 ± 48 min), Emergency Department (ED) crystalloid (4 ± 1 vs. 7 ± 1 L), preICU crystalloid (8 ± 1 vs. 12 ± 1L), ED blood administration (2 ± 1 vs. 6 ± 1 U), GAP CO2 (24 ± 3 vs. 36 ± 3 mmHg), requiring pelvic embolization (9 vs. 47%), and emergency operation (82% vs. 40%). Early predictors identified by MLA of 1° ACS included hemoglobin concentration, GAP CO2 , temperature, and base deficit; and for 2° ACS they included crystalloid, urinary output, and GAP CO2 . The areas under the receiver-operator characteristic curves calculated upon ICU admission are 1° = 0.977 and 2° = 0.983. 1° and 2° ACS patients had similar poor outcomes compared with nonACS patients including ventilator days (1° = 13 ± 3 vs. 2° = 14 ± 3 vs. nonACS = 8 ± 2), multiple organ failure (55% vs. 53% vs. 12%), and mortality (64% vs. 53% vs. 17%). Conclusion: 1° and 2° ACS have similar demographics, injury severity, time to decompression from hospital admit, and bad outcome. 2° ACS is an earlier ICU event preceded by more crystalloid administration. With appropriate monitoring both could be accurately predicted upon ICU admission.

Sweet's syndrome revisited: a review of disease concepts

Abstract: Sweet's syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by a constellation of symptoms and findings: fever, neutrophilia, erythematous and tender skin lesions that typically show an upper dermal infiltrate of mature neutrophils, and prompt improvement of both symptoms and lesions after the initiation of treatment with systemic corticosteroids. Hundreds of patients with this dermatosis have been reported. The manifestations of Sweet's syndrome in these individuals have not only confirmed those originally described by Dr Robert Douglas Sweet in 1964, but have also introduced new features that have expanded the clinical and pathologic concepts of this condition. The history, clinical characteristics, laboratory findings, associated diseases, pathology, and treatment options of Sweet's syndrome are reviewed. The evolving and new concepts of this dermatosis that are discussed include: (i) Sweet's syndrome occurring in the clinical setting of a disease-related malignancy, or medication, or both; (ii) detection of additional sites of extracutaneous Sweet's syndrome manifestations; (iii) discovery of additional Sweet's syndrome-associated diseases; (iv) variability of the composition and/or location of the cutaneous inflammatory infiltrate in Sweet's syndrome lesions; and (v) additional efficacious treatments for Sweet's syndrome.

Amphotericin B: Time for a New “Gold Standard”

Abstract: When introduced in 1959, amphotericin B deoxycholate (AmBD) was clearly a life-saving drug. Randomized studies demonstrating its efficacy were not thought to be necessary, and it was granted indications for many invasive fungal infections. Despite its formidable toxicities, AmBD is thus often used as the primary comparator in studies of invasive fungal infections. Safer lipid-based versions of amphotericin B (AmB) have been introduced, but difficulties with studying these agents generally led to licensure for salvage therapy, not primary therapy. However, the cumulative clinical experience to date with the lipid-based preparations is now adequate to demonstrate that these agents are no less active than AmBD, and, for some infections, it can now be stated that specific lipid-based preparations of AmB are superior to AmBD. Given their superior safety profiles, these preparations can now be considered suitable replacements for AmBD for primary therapy for many invasive fungal infections in clinical practice and research.

Measuring Teachers' Content Knowledge of Language and Reading.

Abstract: In the context of a longitudinal, four-year study of reading instruction in low-performing, high-poverty urban schools, we surveyed teacher knowledge of reading-related concepts, and established a modest predictive relationship between teachers’ knowledge, classroom reading achievement levels, and teachers’ observed teaching competence. There were significant associations among these variables at the third and fourth grade levels. To obtain this result, measures of teacher content knowledge in language and reading were refined in a three-stage process. Our purpose was to explore the type and level of questions that would begin to discriminate more capable from less capable teachers, and that would have a predictive relationship with student reading achievement outcomes. After experimenting with measurement of K-2 teachers’ content knowledge (Form #1), we piloted a Teacher Knowledge Survey with 41 second and third grade teachers in one study site (Form #2). We then refined and expanded the Survey (Form #3) and administered it to 103 third and fourth grade teachers in both project sites. Teachers’ misconceptions about sounds, words, sentences, and principles of instruction were pinpointed so that professional development could address teachers’ needs for insight and information about language structure and student learning.

Roles of transition nuclear proteins in spermiogenesis

Abstract: The transition nuclear proteins (TPs) constitute 90% of the chromatin basic proteins during the steps of spermiogenesis between histone removal and the deposition of the protamines. We first summarize the properties of the two major transition nuclear proteins, TP1 and TP2, and present concepts, based on their time of appearance in vivo and in vitro properties, regarding their roles. Distinct roles for the two TPs in histone displacement, sperm nuclear shaping, chromatin condensation, and maintenance of DNA integrity have been proposed. More definitive information on their roles in spermiogenesis has recently been obtained using mice with null mutations in the Tnp1 or Tnp2 genes for TP1 and TP2, respectively. In these mice, histone displacement and sperm nuclear shaping appear to progress quite normally. Spermatid nuclear condensation occurs, albeit in an abnormal fashion, and the mature sperm of the Tnp -null mutants are not as condensed as wild-type sperm. There is also evidence that sperm from these mutant mice contain an elevated level of DNA strand breaks. The mutant sperm showed several unexpected phenotypes, including a high incidence of configurational defects, such as heads bent back on midpieces, midpieces in hairpin configurations, coils, and clumps, other midpiece defects, reduced levels of proteolytic processing of protamine 2 during maturation, and reduced motility. The two TPs appear partly to compensate for each other as both Tnp1 - and Tnp2 -null mice were able to produce offspring, and appear to have largely overlapping functions as the two mutants had similar phenotypes.

Effect of Pravastatin on Loss of Renal Function in People with Moderate Chronic Renal Insufficiency and Cardiovascular Disease

Abstract: Limited data suggest that HMG-CoA reductase inhibitors (statins) may slow loss of renal function in individuals with chronic renal insufficiency. This study was conducted to determine whether pravastatin reduced rates of loss of renal function in people with moderate chronic renal insufficiency. This was a post hoc subgroup analysis of a randomized double-blind placebo controlled trial. Data were analyzed from the CARE study (a randomized trial of pravastatin versus placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol < 240 mg/dl). Participants with estimated GFR (MDRD-GFR) < 60 ml/min per 1.73 m(2) body surface area at baseline were considered to have moderate chronic renal insufficiency. Multivariate regression was used to calculate rates of decline in MDRD-GFR for individuals receiving pravastatin and placebo, controlling for prospectively determined covariates that might influence rates of renal function loss. Change in renal function could be calculated in 3384 individuals, of whom 690 (20.4%) had MDRD-GFR < 60 ml/min per 1.73 m(2) and were eligible for inclusion. Among all individuals with MDRD-GFR < 60 ml/min per 1.73 m(2)), the MDRD-GFR decline in the pravastatin group was not significantly different from that in the placebo group (0.1 ml/min per 1.73 m(2)/yr slower; 95% CI, -0.2 to 0.4; P = 0.49). However, there was a significant stepwise inverse relation between MDRD-GFR before treatment and slowing of renal function loss with pravastatin use, with more benefit in those with lower MDRD-GFR at baseline (P = 0.04). Rate of change in MDRD-GFR in the pravastatin group was 0.6 ml/min per 1.73 m(2)/yr slower than placebo (95% CI, -0.1 to 1.2; P = 0.07) in those with MDRD-GFR < 50 ml/min, and 2.5 ml/min per 1.73 m(2)/yr slower (95% CI, 1.4 to 3.6 slower; P = 0.0001) in those with MDRD-GFR < 40 ml/min per 1.73 m(2)/yr. Pravastatin also reduced rates of renal loss to a greater extent in participants with than without proteinuria at baseline (P = 0.006). It is concluded that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease, especially those with proteinuria. These findings require confirmation by a large randomized trial conducted specifically in people with chronic renal insufficiency.