Intralenticular abscess caused by Stenotrophomonas maltophilia.
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Abscess↗
Biomedical subjects
D Conrad
Publications and source records attributed to D Conrad.
Electron microscope characterization of CdSe/ZnSe quantum dots based on molecular dynamics structure relaxations
Molecular dynamics simulations using empirical potentials are applied to characterize the structure, the energy relaxation and the stability of pyramidal-shaped quantum dots in the CdSe/ZnSe system. The relaxed structure models are used for a reliable interpretation of electron microscope investigations to analyze the size, the shape and the strain fields of the quantum dots. Though the elastic strains modify the electron microsope image contrast by creating virtual truncations of the pyramids or additional black-white lobes, optimum imaging conditions chosen will reveal the shape and the size of the dots.
Journal Article↗
CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness.
The effects of an anti-CD23 monoclonal antibody (B3B4) in CD23-deficient and CD23-overexpressing mice were compared in a murine model of allergic sensitization. After sensitization and challenge with OA, mice developed increased serum levels of OA-specific IgE and IgG(1) with airway eosinophilia and AHR when compared with nonsensitized animals. Anti-CD23 treatment was studied under two protocols: 10-d OA aerosol exposure and intraperitoneal sensitization followed by aerosol challenge. In both protocols anti-CD23 significantly reduced IgE and IgG(1) levels, abolished eosinophilia, and normalized AHR in BALB/c and wild-type CD23+/+ mice but not in CD23-/- mice. These changes were associated with increases in IFN-gamma and decreases in IL-4 production, suggesting that CD23 binding may affect not only IgE production but also the Th1/Th2 imbalance during the development of allergic AHR. Absence of CD23 in gene-deficient mice significantly enhanced OA-specific IgE and IgG(1) levels, airway eosinophilia, and AHR when compared with CD23+/+ wild-type littermates after sensitization and airway challenge. Sensitized and challenged CD23 transgenic mice also developed eosinophilic airway inflammation and methacholine hyperresponsiveness. However, the extent of AHR, BAL, and tissue eosinophilia in these animals showed a significant negative correlation with levels of CD23 expression on splenic T and B cells, demonstrating a limiting role of CD23 in the development of allergic AHR.
Animals↗
Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase.
The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-dependent nuclear receptor that has been implicated in the modulation of critical aspects of development and homeostasis, including adipocyte differentiation, glucose metabolism and macrophage development and function. PPAR-gamma is activated by a range of synthetic and naturally occurring substances, including antidiabetic thiazolidinediones, polyunsaturated fatty acids, 15-deoxy-delta prostaglandin J2 and components of oxidized low-density lipoprotein, such as 13-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatetraenoic acid (15-HETE). However, the identities of endogenous ligands for PPAR-gamma and their means of production in vivo have not been established. In monocytes and macrophages, 13-HODE and 15-HETE can be generated from linoleic and arachidonic acids, respectively, by a 12/15-lipoxygenase that is upregulated by the TH2-derived cytokine interleukin-4. Here we show that interleukin-4 also induces the expression of PPAR-gamma and provide evidence that the coordinate induction of PPAR-gamma and 12/15-lipoxygenase mediates interleukin-4-dependent transcription of the CD36 gene in macrophages. These findings reveal a physiological role of 12/15-lipoxygenase in the generation of endogenous ligands for PPAR-gamma, and suggest a paradigm for the regulation of nuclear receptor function by cytokines.
Animals↗
Dysregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/MDA6 increases the susceptibility of human leukemia cells (U937) to 1-beta-D-arabinofuranosylcytosine-mediated mitochondrial dysfunction and apoptosis.
The effects of dysregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 on the apoptotic response of U937 monocytic leukemia cells to 1-beta-D-arabinofuranosylcytosine (ara-C) were examined. After a 6-h exposure to 1 microM ara-C, cells stably transfected with a p21WAF1/CIP1 antisense construct were significantly more sensitive to the induction of classic apoptotic morphology, DNA fragmentation, caspase-3 activation, poly(ADP-ribose) polymerase degradation, and underphosphorylation of the retinoblastoma protein (pRb) than their empty-vector counterparts. Enhanced susceptibility of antisense-expressing cells to ara-C was accompanied by a corresponding reduction in clonogenic and suspension culture growth. The increased sensitivity of these cells to ara-C-mediated lethality could not be attributed to cytokinetic perturbations, nor did ara-CTP formation or (ara-C)DNA incorporation differ significantly between the cell lines. Moreover, synchronization of p21 antisense-expressing cells in S-phase by aphidicolin block resulted in a further increase in ara-C-mediated apoptosis, suggesting enhanced drug sensitivity of the S-phase cell fraction. After exposure to ara-C, p21 antisense-expressing cells displayed a greater decline in mitochondrial membrane potential (deltapsi(m)) and generation of reactive oxygen species than their empty-vector counterparts, as well as early potentiation (e.g., within 2-4 h) of cytochrome c release into the cytosolic S-100 fraction. Lastly, ara-C-mediated increases in mitogen-activated protein kinase activity over basal levels were attenuated in p21 antisense-expressing cells. Collectively, these findings indicate that dysregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 increases the susceptibility of U937 human leukemia cells to ara-C-related lethality, and this phenomenon occurs as a relatively early event that is independent of cell cycle or pharmacodynamic factors and is associated with mitochondrial perturbations implicated in activation of the apoptotic protease cascade.
Antimetabolites, Antineoplastic↗
TEM characterization of self-organized CdSe/ZnSe quantum dots.
CdSe quantum dots (QDs) grown on ZnSe were investigated by various transmission electron microscopy (TEM) techniques including diffraction contrast imaging, high-resolution and analytical transmission electron microscopy both of plan-view as well as cross-section specimens. The size of the QDs ranges from about 5-50 nm, where from the contrast features in plan-view imaging two classes can be differentiated. In the features of the smaller dots there is no inner fine structure resolvable. The larger ones exhibit contrast features of fourfold symmetry as expected for pyramid-like islands. Corresponding simulations of diffraction contrast images of truncated CdSe pyramids with the edges of the basal plane orientated parallel to <100> are in relatively good agreement with this assumption. In TEM diffraction contrast imaging of cross-section samples the locations of the quantum dots are visualized by additional dark contrast features. The QDs have a distinct larger extension in growth direction compared to the almost uniformly thick CdSe wetting layer. The presence of the CdSe QDs was also confirmed by energy-dispersive X-ray spectroscopy.
Journal Article↗
Instillation of calf lung surfactant extract (calfactant) is beneficial in pediatric acute hypoxemic respiratory failure. Members of the Mid-Atlantic Pediatric Critical Care Network.
OBJECTIVE: Prospective study of the efficacy of calf lung surfactant extract in pediatric respiratory failure. DESIGN: Multi-institutional, prospective, randomized, controlled, unblinded trial. SETTING: Eight pediatric intensive care units (ICU) of tertiary medical centers. PATIENTS: Forty-two children with acute hypoxemic respiratory failure characterized by diffuse, bilateral pulmonary infiltrates, need for ventilatory support, and an oxygenation index of >7. INTERVENTION: Instillation of intratracheal surfactant (80 mL/m2). MEASUREMENTS AND MAIN RESULTS: Ventilator parameters, arterial blood gases, and derived oxygenation and ventilation indices were recorded before and at intervals after surfactant administration. Complications and outcome measures, including mortality, duration of mechanical ventilation, and length of pediatric ICU and hospital stay, were also examined. Patients who received surfactant demonstrated rapid improvement in oxygenation and, on average, were extubated 4.2 days (32%) sooner and spent 5 fewer days (30%) in pediatric intensive care than control patients. There was no difference in mortality or overall hospital stay. Surfactant administration was associated with no serious adverse effects. CONCLUSIONS: Administration of calf lung surfactant extract, calfactant, appears to be safe and is associated with rapid improvement in oxygenation, earlier extubation, and decreased requirement for intensive care in children with acute hypoxemic respiratory failure. Further study is needed, however, before widespread use in pediatric respiratory failure can be recommended.
Adolescent↗
Chronic varicella-zoster virus epithelial keratitis in patients with acquired immunodeficiency syndrome.
OBJECTIVE: To characterize further a chronic epithelial keratitis caused by varicella-zoster virus infection in patients with acquired immunodeficiency syndrome (AIDS). METHODS: Patients with AIDS and chronic epithelial keratitis associated with varicella-zoster virus from 3 institutions were identified. Patient records were reviewed retrospectively for the following data: medical and demographic characteristics, techniques of diagnosis, physical findings, course, response to treatment, and outcome. RESULTS: Sixteen patients were studied. CD4+ T-lymphocyte cell counts were available in 11 patients, with a median of 0.034 x 10(9)/L (range, 0-0.094 x 10(9)/L). Two patients had no history of a zosteriform rash. In the remaining patients, the interval between rash and keratitis ranged from 0 days to 6 years. In all cases, the keratitis was chronic and characterized by gray, elevated, dendriform epithelial lesions that stained variably with fluorescein and rose bengal. The peripheral and midperipheral cornea was most commonly affected, and, in 13 of the 16 patients, the lesions crossed the limbus. Pain was a prominent feature, occurring in 12 of 16 patients. In 9 of 12 patients tested, varicella-zoster virus was identified by culture, direct fluorescent antibody testing, polymerase chain reaction testing, or a combination of these studies, with direct fluorescent antibody testing (6 of 8 positive results) and polymerase chain reaction testing (3 of 3 positive results) appearing to be the most sensitive. Response to antiviral medication was variable. CONCLUSIONS: In patients with AIDS, varicella-zoster virus may cause a chronic infection of the corneal epithelium. The keratitis is characterized by dendriform lesions, prolonged course, and frequently by extreme pain. It can occur without an associated dermatitis.
Acquired Immunodeficiency Syndrome↗
Cytomegalovirus retinitis, human immunodeficiency virus antibody positivity and normal T helper cell numbers.
We describe a 46-year-old man in whom retinitis was diagnosed as his initial HIV and AIDS defining illness. A diagnosis of CMV infection was made based on the clinical appearance of the fundus and confirmed by DNA polymerase chain reaction (PCR) on his vitreous biopsy. His CD4+ T lymphocyte count at the time was 580 x 10(6)/l (16%) with a CD4:CD8 ration of 0.28. He had a splenectomy following trauma more than 20 years earlier. He responded very well to intravenous and oral ganciclovir and remains recurrence-free almost 2 years later. This case and others highlight two issues: (i) CMV retinitis in HIV positive is not confined to those with very low CD4+ T lymphocyte counts; (ii) previous splenectomy may have an impact on CD4+ cell numbers and function.
AIDS-Related Opportunistic Infections↗
Conscious experience and information.
Conscious experience, our main source of information, has special properties. Primary among them is privacy, or privileged access by persons to their own conscious states. The consequent theoretical and practical problems for research on both consciousness and information are delineated.
Cognition↗
The complications of trauma and their associated costs in a level I trauma center.
OBJECTIVES: To estimate the expected costs for acute trauma care, to quantify the costs associated with the development of complications in injury victims, and to determine the deficit incurred by patients in whom complications develop. DESIGN: A retrospective, cohort design. SETTING: A referral trauma center. PATIENTS: A total of 12,088 patients admitted to a single regional trauma center during a period of 5 years. INTERVENTIONS: This is an observational study, and no interventions specific to this study are included in the design. MAIN OUTCOME MEASURES: (1) The expected costs for injury victims based on readily available clinical data. (2) The costs associated with the most important complications of trauma. (3) The effect of complications on inadequate reimbursement for trauma care. RESULTS: The expected costs were estimated using a linear model incorporating demographic variables and measures of injury severity. The expected costs averaged $14,567, and the observed costs averaged $15,032. Six complications were important predictors of cost. These included adult respiratory distress syndrome, acute kidney failure, sepsis, pneumonia, decubitus ulceration, and wound infections. For 1201 individuals with these complications, the predicted costs averaged $23,266 and the observed costs averaged $47,457. The mean excess costs for a single complication ranged from $6669 to $18,052. Multiple complications led to greater increases in excess cost, averaging $110,007 for the 62 patients with 3 or more complications. Costs exceeded reimbursement to a much greater degree in those in whom any of the 6 complications developed. CONCLUSION: Expected hospital costs can be estimated using admission clinical data. Each of 6 complications was associated with enormous increases in costs, indicating their importance as a cause of avoidable expenditures in injury victims and identifying situations in which reimbursement may not be adequate.
Cohort Studies↗
Cytomegalovirus-associated acute retinal necrosis syndrome.
PURPOSE: To describe a case of acute retinal necrosis syndrome in which a polymerase chain reaction-based assay provided evidence for cytomegalovirus as the causative agent of the syndrome. METHODS: Polymerase chain reaction-based assays were used to analyze a vitreous aspirate from a 70-year-old man with acute retinal necrosis syndrome. The specimen was tested for cytomegalovirus, varicella-zoster virus, and herpes simplex virus type 1 and type 2. RESULTS: The polymerase chain reaction assay for cytomegalovirus was positive, and polymerase chain reaction assays for varicella-zoster virus and herpes simplex virus type 1 and type 2 were negative. CONCLUSION: Cytomegalovirus may be a causative agent of acute retinal necrosis syndrome.
Aged↗
Does fluoridation reduce the use of dental services among adults?
OBJECTIVES: The authors determine whether prevention influences the use of health services. Fluoridation's effect on restorative dental demand among 972 Washington state employees and spouses, aged 20 to 34 years, in two fluoridated communities and a nonfluoridated community was examined. METHODS: At baseline, adults were interviewed by telephone, and oral assessments were conducted to measure personal characteristics, lifetime exposure to fluoridated water, oral disease, and the quality of restorations. Adults were followed for 2 years to measure dental demand from dental claims. Each adult's baseline and claims data were linked with provider and practice variables collected from the dentist who provided treatment. RESULTS: Relative to adults with no lifetime exposure to fluoridated water, adults drinking fluoridated water for half or more of their lives had less disease at baseline and a lower but nonsignificant probability of receiving a restoration in the follow-up period. In the 2-year follow-up period, however, more than half of the restorations were performed to replace fillings of satisfactory or ideal quality at baseline. When only teeth with decay and unsatisfactory fillings at baseline were considered, adults with high fluoridation exposure had a lower probability of receiving a restoration than adults with no exposure. Market effects also were detected in demand equations; relative to adults in the nonfluoridated community, adults residing in the fluoridated community with a large dentist supply received a greater number of restorations, suggesting potential supplier-induced demand from less disease and fewer patients. CONCLUSIONS: Among adults aged 20 to 34 years with private dental insurance, fluoridation reduces oral disease but may or may not reduce use of restorative services, depending on dentists' clinical decisions.
Adult↗
The relationship between price of services, quality of care, and patient time costs for general dental practice.
OBJECTIVE: To examine the relationships between price of services, quality of care, and patient time costs in private practices of general dentists. DATA SOURCE/STUDY SETTING: In October 1992, a 3.7 percent sample of eligible general dentists in part-time or full-time private practice in 1991 was randomly drawn from a sampling frame tailored from data gathered by the 1991-1992 American Dental Association Distribution of Dentists census of all United States dentists. DATA COLLECTION: A mail survey was used to collect data on dentist demographic characteristics, dental practice characteristics practice finances, and insurance. The survey was completed and returned by 3,048 general dentists (77 percent response rate). Local area population characteristics were obtained from secondary sources. STUDY DESIGN: Two-stage least squares regression was used to evaluate the structural relationships between price of services, quality of care, and time costs to patients. Structural equations were estimated for four different quality of care measures and two time costs. PRINCIPAL FINDINGS: Price of services and quality of care were significantly related to each other. Higher quality of care was associated with higher price of services and, reciprocally, higher price of services was associated with higher quality of care. Shorter waits for a new patient appointment were associated with higher prices. Higher price of services, lower quality of care, and longer waits for a new patient appointment were related to shorter in-office waiting time. CONCLUSIONS: The implication of these findings is that if price of services is constrained, then the quality of care provided by the dentist may also be reduced.
Fees, Dental↗
Consciousness, privacy, and information.
The challenges for a scientific study of conscious experience are discussed, as well as the importance of such research for the foundations of information science. A three pronged approach to the investigation of consciousness and its functions is suggested.
Consciousness↗
Calf's lung surfactant extract in acute hypoxemic respiratory failure in children.
OBJECTIVE: Open-label trial of the safety and short-term efficacy of calf's lung surfactant in pediatric respiratory failure. DESIGN: Multi-institutional, uncontrolled, observational trial. SETTING: Six pediatric intensive care units of tertiary medical centers. PATIENTS: Twenty-nine children with acute hypoxemic respiratory failure, characterized by diffuse, bilateral, pulmonary infiltrates, need for ventilator support, and an oxygenation index of > or = 7. INTERVENTIONS: Up to four doses of intratracheal surfactant (80 mL/m2). MEASUREMENTS AND MAIN RESULTS: Ventilator parameters, arterial blood gases, and derived oxygenation and ventilation indices were recorded before, and at intervals after, surfactant administration. Complications and outcome measures were also noted. There was immediate improvement in oxygenation and moderation of ventilator support associated with surfactant administration in 24 of 29 patients. A modest but statistically insignificant effect was seen with subsequent doses. The only complications occurred in three patients who developed airleaks, two of which were coincident with surfactant administration. The overall mortality rate was 14%, which compares favorably with other published series. CONCLUSIONS: Administration of calf's lung surfactant appears to be safe and is associated with rapid improvement in oxygenation and moderation of ventilator support in children with acute hypoxemic respiratory failure. These results set the stage for a randomized, controlled study.
Acute Disease↗
Frustrating patient visits.
OBJECTIVES: This study, part of a national mail survey of dentist malpractice liability claims, reports the reliability and validity of a new 22-item instrument measuring frustrating patient visits. METHODS: The items were subjected to factor analysis and subscales constructed. Reliability was assessed using Cronbach's alpha. Validity was assessed by comparing subscale scores to self-reports of satisfaction and liability claims. RESULTS: Factor analysis revealed four subscales representing unpleasant feelings, lack of communication, compliance, and practice organization (alpha = 0.60-0.86). Compliance was the most important factor. Subscale scores were related to satisfaction with practice and the proportion of patient visits in the practice that were frustrating to the dentist. Dentists who reported frustrating patient visits as quite typical of their practices were more likely to have had a malpractice liability claim within the last five years. CONCLUSION: This instrument may be of value in detecting patient-dentist communication difficulties that are the precursor to liability claims.
Communication↗
Managing care, incentives, and information: an exploratory look inside the "black box" of hospital efficiency.
OBJECTIVE: We sought to estimate the impact of individual dimensions of hospitals' managed care strategies on the cost per hospital discharge. STUDY SETTING/DATA SOURCES: Thirty-seven member hospitals of seven health systems in the Pacific, Rocky Mountain, and Southwest regions of the United States were studied. STUDY DESIGN: Separate cross-sectional regression analyses of 21,135 inpatient discharges were performed in 1991 and 23,262 discharges in 1992. The multivariate model was estimated with hospital cost per discharge as the dependent variable. Model robustness was checked by comparing regression results at the individual discharge level with those at the level of the hospital/clinical condition pair. DATA COLLECTION/EXTRACTION METHODS: Information on hospitals' managed care strategies was provided by mail and phone survey of key informants in 1991 and 1992. Other hospital characteristics were collected from AHA Annual Survey data, and discharge data from hospital abstracting systems. PRINCIPAL FINDINGS: The pooled discharge analysis indicated three dimensions of hospital managed care strategy that consistently related to lower costs per hospital discharge: the proportion of hospital revenues derived from per case or capitation payment, the hospital's mechanisms for sharing information on resource consumption with clinicians, and the use of formalized, systematic care coordination mechanisms. CONCLUSIONS: Three strategies appear to hold promise for enhancing the efficiency of inpatient resource use: (1) "fixed price" hospital payment incentives, (2) hospital approaches to sharing resource use information with clinicians, and (3) the application of formal care management mechanisms for specific clinical conditions.
Aged↗