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J Daley

Publications and source records attributed to J Daley.

At least 109 records · Page 6Linked to original sources

Follicular lymphomas can be induced to present alloantigen efficiently: a conceptual model to improve their tumor immunogenicity.

In the tumor-bearing host, T cells invariably fail to induce a clinically significant antitumor immune response. Although model systems support the existence of tumor peptide antigens, the molecular interactions critical for antigen presentation by the tumor cell remain unresolved. Here, we demonstrate that human follicular lymphoma cells are highly inefficient at presenting alloantigen despite their strong expression of major histocompatibility complex and low-to-intermediate expression of some adhesion and B7 costimulatory molecules. Activation of follicular lymphoma cells via CD40 induces or up-regulates both adhesion and B7 costimulatory molecules essential to repair this defect. More importantly, once primed, alloreactive T cells efficiently recognize unstimulated follicular lymphoma cells. Thus, correction of defective tumor immunity requires not only expression of major histocompatibility complex but also sufficient expression of multiple adhesion and costimulatory molecules.

Antigen-Antibody Reactions↗

Medical patients' assessments of their care during hospitalization: insights for internists.

OBJECTIVE: To assess, from the patient's perspective, selected aspects of the quality of inpatient hospital care in the United States. DESIGN: A cross-sectional survey, using telephone interviews of patients discharged from the medical services of a probability sample of 62 public and private, nonprofit, nonfederal acute care hospitals in the United States. The participating patients reported; discrete, clinically important elements of hospital care; preferences for involvement in care; health status; sociodemographic characteristics; and overall satisfaction with their hospitalization. PATIENTS/PARTICIPANTS: 2,839 patients drawn as a probability sample. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 32 of the 50 questions about potential problems encountered during hospitalization, at least 10% of the patients gave a response indicating a problem. One-third of the patients having a physician (31.8%) reported that that physician did not care for them during hospitalization. Other frequently reported problems included not receiving information about the hospital routine (45.1%), not being told whom to ask for help (33.9%), having pain that could have been relieved by more prompt attention (19.9%), and not being given adequate information and guidance about activities and care after discharge from the hospital (21.4-36.1%). Most patients preferred to be informed about important aspects of their care (94.7%), but their preferences for involvement in care varied widely. CONCLUSIONS: Information from hospitalized medical patients identified several areas of concern that should be the focus of attention and could lead to systematic restructuring of hospital-based care.

Adult↗

Using severity-adjusted stroke mortality rates to judge hospitals.

Mortality rates are commonly used to judge hospital performance. In comparing death rates across hospitals, it is important to control for differences in patient severity. Various severity tools are now actively marketed in the United States. This study asked whether one would identify different hospitals as having higher- or lower-than-expected death rates using different severity measures. We applied 11 widely-used severity measures to the same database containing 9407 medically-treated stroke patients from 94 hospitals, with 916 (9.7%) in-hospital deaths. Unadjusted hospital mortality rates ranged from 0 to 24.4%. For 27 hospitals, observed mortality rates differed significantly from expected rates when judged by one or more, but not all 11, severity methods. The agreement between pairs of severity methods for identifying the worst 10% or best 50% of hospitals was fair to good. Efforts to evaluate hospital performance based on severity-adjusted, in-hospital death rates for stroke patients are likely to be sensitive to how severity is measured.

Adolescent↗

A heterogeneous population of alpha 1 adrenergic receptors mediates contraction of human corpus cavernosum smooth muscle to norepinephrine.

In this study we investigated the physiological properties and binding characteristics of alpha-1 adrenergic receptor (alpha 1-AR) in human corpus cavernosum (HCC) in order to identify alpha 1-AR subtypes at the functional protein level. Exposure of tissue strips to norepinephrine (NE) caused concentration-dependent contractions that were partially and noncompetitively inhibited by 10 to 100 microM. of chloroethylclonidine (CEC), an alkylating agent that specifically and irreversibly inactivates alpha 1B-AR and alpha 1C-AR subtypes. Norepinephrine-induced contractions were competitively and effectively inhibited with WB 4101, a competitive, high-affinity antagonist for alpha 1A-AR and alpha 1C-AR subtypes. The CEC-insensitive receptor subtypes bound WB 4101 with high affinity, suggesting the presence of alpha 1A-AR in HCC. Binding of [3H]prazosin and 2-[beta-(4-hydroxy-3-[125I]iodophenyl)-ethylaminomethyl]-tetralone ([125I]HEAT) to membranes of HCC treated with or without CEC demonstrated the presence of two subpopulations: a CEC-sensitive receptor population (40 to 50%), which may represent inactivation of the alpha 1B-AR and alpha 1C-AR subtypes, and a CEC-resistant receptor subpopulation, which is probably the alpha 1A-AR subtype. The physiological and biochemical properties of alpha 1-AR in HCC clearly suggest that the NE-induced contraction of HCC smooth muscle is mediated by more than one alpha 1-AR subtype. It is likely that two or possibly three receptor subtypes are involved in mediating the contraction. Further, it is possible that NE-mediated contraction of trabecular smooth muscle requires synergistic receptor-receptor receptor interactions at the second messenger or at the receptor protein level.

Alkylating Agents↗

Possible role of Na(+)-K(+)-ATPase in the regulation of human corpus cavernosum smooth muscle contractility by nitric oxide.

1. This study was designed to determine the role of sodium-potassium adenosine triphosphatase (Na(+)-K(+)-ATPase) in the regulation of human corpus cavernosum smooth muscle contractility by nitric oxide (NO). In addition, we determined if the modulation of Na(+)-K(+)-ATPase activity by NO is dependent on the increase in intracellular cyclic GMP concentration. 2. The effect of NO donors, sodium-nitroprusside (SNP) and S-nitroso-glutathione (S-NO-Glu), and a permeable cyclic GMP analogue, 8-bromo-cyclic GMP, on Na(+)-K(+)-ATPase activity (measured as ouabain-sensitive 86Rb-uptake) was studied in human cultured corpus cavernosum smooth muscle cells (HCCSMC). In addition, the effect of the cyclic GMP lowering agent, methylene blue, on NO-induced increase in Na(+)-K(+)-ATPase activity was studied. 3. SNP (1 microM) caused time-dependent increases in ouabain-sensitive Rb-uptake (33-72%) over 2-20 min in HCCSMC. The stimulation of ouabain-sensitive Rb-uptake by SNP was concentration-dependent (30 and 102% with 0.1 and 1 microM SNP, respectively). Similarly, significant increases in ouabain-sensitive Rb-uptake were obtained with 1 and 10 microM S-NO-Glu. In contrast, incubation of HCCSMC with 8-bromo-cyclic GMP (100 microM) did not increase ouabain-sensitive Rb-uptake. 4. S-NO-Glu induced-increase in intracellular cyclic GMP synthesis, but not the increase in ouabain-sensitive Rb-uptake, was completely inhibited by methylene blue in HCCSMC. 5. The Na(+)-K(+)-ATPase inhibitor, ouabain, caused a concentration-dependent increase in tension (0.5 to 2 fold) in tissues contracted with 15 mM KCl. SNP and S-NO-Glu caused a concentration-dependent relaxation (concentration required to cause half maximal relaxation (ED50) = 0.04 and 0.2 microM, respectively) of HCC strips contracted with 15 mM K+. Ouabain (0.1 to 10 microM) inhibited the response to SNP and S-NO-Glu by shifting the concentration-response curves to the right and preventing full smooth muscle relaxation.6. These results indicate that the activity of Na+-K+-ATPase modulates the contractility of HCC smooth muscle, and that NO stimulates Na+-K+-ATPase activity in HCCSMC independently of its ability to increase the intracellular cyclic GMP concentration. They also suggest that stimulation of Na+-K+-ATPase activity plays an important role in NO-induced relaxation of HCC smooth muscle

Cells, Cultured↗

Costs of potential complications of care for major surgery patients.

We examined computerized hospital discharge abstract data from 372,680 major surgery patients admitted to 404 California acute care hospitals in 1988 to identify potential complications of care. At least one potential in-hospital complication occurred for 10.8% of patients. Patients with complications were older and more likely to die in-hospital (9.4% compared to 1.0%, P < 0.0001). On average, patients with complications had longer stays (13.5 versus 5.4 days, p < 0.0001) and higher total charges ($30,896 versus $9,239, p < 0.0001). After adjusting for demographic, clinical, and hospital factors, patients with potential complications averaged $16,023 higher total hospital charges than uncomplicated patients. Complications were associated with 96.6% (95% confidence interval = 95.2%, 98.0%) higher hospital charges after adjusting for these factors. Across all patients, complications were related to over $647 million in additional total hospital charges for these major surgery patients.

California↗

The National Veterans Administration Surgical Risk Study: risk adjustment for the comparative assessment of the quality of surgical care.

BACKGROUND: The use of surgical outcome in the comparative assessment of the quality of surgical care is predicted on the development of proper models that adjust for the severity of the preoperative risk factors of the patient. The National Veterans Administration Surgical Risk Study was designed to collect reliable, valid data about patient risk and outcome for major surgery in the Veterans Health Administration (VHA) and to report comparative risk-adjusted surgical morbidity and mortality rates for surgical services in VHA. This study describes the rationale and methods used in the Risk Study and reports on the frequency distribution of the data elements that will be used in the development of risk-adjusted reporting of surgical outcome. STUDY DESIGN: This study was a prospective observational study in which dedicated nurses collected preoperative, intraoperative, and outcome data on patients undergoing noncardiac operations using general, spinal, and epidural anesthesia in 44 Veterans Administration Medical Centers. Outcome measures included all cause mortality within the 30 days after the index procedure and 21 major morbidities. RESULTS: Eighty-three thousand nine hundred fifty-eight cases meeting inclusion criteria were entered in the study between October 1, 1991 and December 31, 1993. Ninety-seven percent of patients were men, with a mean age of 60.1 +/- 13.6 (standard deviation) years. The most common preoperative risk factors were smoking (40.7 percent) and hypertension (36.1 percent). Of the patients, 84.6 percent had one or more risk factors. The most common procedures were transurethral resection of the prostate gland (6.7 percent), total knee replacement (3.1 percent), thromboendarterectomy (2.4 percent), partial colectomy (2.2 percent), and total hip replacement (2 percent). The unadjusted mortality rate was 3.1 percent at 30 days. The most common postoperative morbidities were pneumonia (3.6 percent), urinary tract infection (3.5 percent), and failure to wean from the ventilator at 48 hours postoperatively (3.2 percent). Seventeen percent of the patients have one or more major complications. CONCLUSIONS: The Veterans Health Administration has successfully implemented an outcome reporting system for major surgery that prospectively collects patient risk and outcome information reliably and validly. Risk adjustment models and comparative hospital-specific rates of risk-adjusted outcomes are currently being developed.

Aged↗

Racial variation in cardiac procedure use and survival following acute myocardial infarction in the Department of Veterans Affairs.

OBJECTIVE: To examine whether blacks admitted to Veterans Affairs Medical Centers (VAMCs) with an acute myocardial infarction (AMI) are less likely than whites to undergo cardiac catheterization or coronary revascularization procedures and to determine the impact of these differences on patient survival. DESIGN: A retrospective observational study of inpatient discharge abstracts from the Veterans Health Administration (VHA). SETTING: All one hundred fifty-eight acute care hospitals in the VHA. PATIENT POPULATION: Male veterans (n = 33,641) discharge from VAMCs with an International Classification of Diseases, Ninth Revision, Clinical Modification code for AMI from January 1, 1988, to December 31, 1990. INTERVENTION: None. MAIN OUTCOME MEASURES: The use of cardiac catheterization, coronary angioplasty, and/or bypass surgery in the 90 days after admission for AMI, and survival at 30 days, 1 year, and 2 years. MAIN RESULTS: Adjusting for patient and hospital characteristics, blacks with an AMI were 33% less likely than whites to undergo cardiac catheterization, 42% less likely to receive coronary angioplasty, and 54% less likely to receive coronary bypass surgery. Among patients who underwent catheterization, blacks were also less likely than whites to have a subsequent cardiac revascularization procedure. Adjusted 30-day survival for blacks was significantly greater than for whites. One- and 2-year survival rates after AMI were not significantly different between blacks and whites. CONCLUSIONS: In a health care system designed to provide equivalent availability of care to all eligible patients, blacks received substantially fewer cardiac procedures after AMI than whites. Despite undergoing fewer interventional procedures, blacks had better short-term and equivalent intermediate survival rates compared with whites.

Black or African American↗

Criteria by which to evaluate risk-adjusted outcomes programs in cardiac surgery.

Risk adjustment models for hospitalized patients are most advanced for the assessment of the clinical outcome of cardiac procedures, and for coronary artery bypass grafting in particular. The goal of being able to use outcomes as a credible indicator of quality of care has stimulated the development of several programs that use reliable, valid patient data collected during the surgical episode to adjust outcomes for the severity of illness. Several criteria that are useful in the assessment of risk adjustment methods for outcome and quality-of-care investigations are discussed in detail and five of these programs are compared. The programs have more similarities than differences and identify many of the same patient characteristics predictive of a higher likelihood of mortality in the period immediately after operation. Whether persistent differences in mortality after risk adjustment across institutions or individual surgeons, or both, may ultimately be attributed to the process and structure of care needs further study and investigation. Similar methods should be applied to other outcomes of importance to patients, their families, and their physicians, such as surgically related morbidity, functional status, quality of life, costs, and patient-reported perceptions of the nontechnical aspects of their care.

Cardiac Surgical Procedures↗

Provider perceptions in using outcomes data to improve clinical practice.

In this article we report on the perceptions of health care providers concerning the use of health care outcomes. These perceptions were identified during two afternoon workshops at the symposium on outcomes data held in Keystone, Colorado, in June 1994. The overall goal of these workshops was to explore the potential use of outcomes data within the clinical practice setting. The attitudes and concerns of several key providers formed the framework for the workshop discussions. The strengths and weaknesses associated with using risk-adjusted outcomes data, both to assess and to improve quality of patient care, were debated within the workshop groups. Overall, conference participants agreed that the risk-adjusted outcomes of cardiac care could be used both to assess and to improve the quality of patient care. The research to date, however, represents only a first step toward this goal. The meeting participants challenged the research community to improve on the measures currently available, with the goal of providing clinicians better information to improve the "art" of medicine.

Attitude of Health Personnel↗

Identifying complications of care using administrative data.

The Complications Screening Program (CSP) is a method using standard hospital discharge abstract data to identify 27 potentially preventable in-hospital complications, such as post-operative pneumonia, hemorrhage, medication incidents, and wound infection. The CSP was applied to over 1.9 million adult medical/surgical cases using 1988 California discharge abstract data. Cases with complications were significantly older and more likely to die, and they had much higher average total charges and lengths of stay than other cases (P < 0.0001). For most case types, 13 chronic conditions, defined using diagnosis codes, increased the relative risks of having a complication after adjusting for patient age. Cases at larger hospitals and teaching facilities generally had higher complication rates. Logistic regression models to predict complications using demographic, administrative, clinical, and hospital characteristics variables, had modest power (C statistics = 0.64 to 0.70). The CSP requires further evaluation before using it for purposes other than research.

Adult↗

Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B-lymphocyte development.

CD19 is a B-cell-specific member of the immunoglobulin superfamily expressed from early pre-B-cell development until plasma cell differentiation. In vitro studies demonstrate that the CD19 signal transduction molecule can serve as a costimulatory molecule for activation through other B-lymphocyte cell surface molecules. However, much remains to be known regarding how CD19 functions in vivo and whether CD19 has different roles at particular stages of B-cell differentiation. Therefore, transgenic mice overexpressing the human CD19 (hCD19) gene were generated to determine whether this transgene would be expressed in a B-lineage-specific fashion and to dissect the in vivo role of CD19 in B-cell development and activation. Expression of the human transgene product was specifically restricted to all B-lineage cells and appeared early in development as occurs with hCD19. In addition, expression of hCD19 severely impaired the development of immature B cells in the bone marrow, with dramatically fewer B cells found in the spleen, peripheral circulation, and peritoneal cavity. The level of hCD19 expressed on the cell surface correlated directly with the severity of the defect in different transgenic lines. These results demonstrate that the hCD19 gene is expressed in a lineage-specific fashion in mice, indicating that the hCD19 gene may be useful for mediating B-lineage-specific expression of other transgene products. In addition, these results indicate an important role for the lineage-specific CD19 molecule during early B-cell development before antigen-dependent activation.

Aging↗

Chronic conditions and risk of in-hospital death.

OBJECTIVE: This study examined the relationship of in-hospital death and 13 conditions likely to have been present prior to the patient's admission to the hospital, defined using secondary discharge diagnosis codes. DATA SOURCES AND STUDY SETTING: 1988 California computerized hospital discharge abstract data, including 24 secondary diagnosis coding slots, from all general, acute care hospitals. STUDY DESIGN: The odds ratio for in-hospital death associated with each of 13 chronic conditions was computed from a multivariable logistic regression using patient age and all chronic conditions to predict in-hospital death. DATA EXTRACTION: All 1,949,276 general medical and surgical admissions of persons over 17 years of age were included. Patients were assigned to four groups according to the mortality rate of their reason for admission; some analyses separated medical and surgical hospitalizations. PRINCIPAL FINDINGS: Overall mortality was 4.4 percent. For all cases, mortality varied by chronic condition, ranging from 5.3 percent for coronary artery disease to 18.6 percent for nutritional deficiencies. The odds ratios associated with the presence of a chronic condition were generally highest for patients in the rare mortality group. Although chronic conditions were more commonly listed for medical patients, the associated odds ratios were generally higher for surgical patients, particularly in lower mortality groups. CONCLUSIONS: Studies examining death rates need to consider the influence of chronic conditions. Chronic conditions had a particularly significant association with the likelihood of death for admission types generally associated with low mortality rates and for surgical hospitalizations. The accuracy and completeness of discharge diagnoses require further study, especially relating to chronic illnesses.

Adolescent↗

Alterations in Ca2+ signal transduction in critically ill surgical patients.

BACKGROUND: Despite improvements in supportive care and pharmacologic therapies, sepsis and related disorders such as systemic inflammatory response syndrome (SIRS) continue to be a leading cause of death in the intensive care unit. We hypothesized that immune dysfunction in this setting may in part be mediated at the level of early signal transduction in monocytes and neutrophils as manifested by changes in intracellular free Ca2+. METHODS: Monocytes and neutrophils were isolated from patients in the intensive care unit who met the criteria for SIRS and from normal volunteers. Cells were loaded with the Ca(2+)-sensitive fluorescent dye Indo-1 and stimulated with the chemotactic peptide f-Met-Leu-Phe (fMLP). Changes in intracellular calcium ion concentration were measured by flow cytometry. RESULTS: Patient monocytes exhibited a decreased Ca2+ flux (43% +/- 3.1%) as compared with normal monocytes (63% +/- 2.5%) (p < 0.05). Patient neutrophils also exhibited a decreased Ca2+ flux in response to fMLP of 58% +/- 3.7% versus 69.3% +/- 3.1% for normal neutrophils (p < 0.05). Incubation of patient cells in normal plasma reversed this dysfunction and showed an improved Ca2+ flux to 60% +/- 2.7% for monocytes and 71% +/- 3.7% for neutrophils (p < 0.05). Conversely, calcium flux was decreased in both normal monocytes (42.3% +/- 3.1%) and normal neutrophils (55.4% +/- 3.8%) after incubation in SIRS patient plasma (p < 0.05). Incubation of normal monocytes and neutrophils in interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor, or lipopolysaccharide did not show a statistically significant alteration in calcium flux in response to fMLP. CONCLUSIONS: Patients with SIRS exhibit alterations in early signal transduction after stimulation with fMLP in monocytes and neutrophils. This effect appears to be mediated by a soluble factor because the defect in SIRS patient cells can be reversed by incubation in normal plasma and normal cells appear to acquire this defect after incubation in patient plasma. Further studies are underway to identify the factor or factors responsible for this functional defect.

Adult↗

Using administrative data to screen hospitals for high complication rates.

Medicare's Peer Review Organizations (PROs) now are required to work with hospitals to improve patient outcomes. Which hospitals should be targeted? We used 1988 California discharge data to identify hospitals with higher-than-expected rates of complications in six adult, medical-surgical patient populations. Relative hospital complication rates generally were correlated across clinical areas, although correlations were lower between medical and surgical case types. Higher relative rates of complications were associated with larger size, major teaching facilities, and provision of open heart surgery, as well as with coding more diagnoses per case. Complication rates generally were not related significantly to hospital mortality rates as calculated by the Health Care Financing Administration. Different hospitals may be chosen for quality review depending on the method used to identify poor outcomes.

Aged↗