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Biomedical subjects

M Riedinger

Publications and source records attributed to M Riedinger.

13 recordsLinked to original sources
PubMed1999

CD4 T cell traffic control: in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles.

We report here that CD40- but not lipopolysaccharide (LPS)-activated murine dendritic cells (DC) express OX40-ligand (OX40L) as has been reported in humans. To understand how OX40 ligation affects differentiation of CD4 T cells at the time of priming, we constitutively expressed OX40L on DC using the DC-specific promoter of CD11c. Transgenic mice showed greatly increased numbers of CD4 but not CD8 T cells in their B cell areas. This effect was to a great extent immunization dependent, as spleen and lymphoid tissue with no germinal center reactions from mice which had not been deliberately immunized did not show marked CD4 T cell accumulation. The increased numbers of CD4+ CD62low cells in transgenic mice suggest that it is activated CD4 T cells that accumulate within B cell follicles. These data are consistent with the notion that physiological engagement of OX40 (CD134) on activated CD4 T cells either initiates their migration into or causes them to be retained in B follicles. In contrast, LPS-treated CD did not up-regulate OX40L expression. This dichotomy provides a molecular explanation of how DC might integrate environmental and accessory signals to control cytokine differentiation and migration in CD4 effector cells.

Animals↗
PubMed1997

Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo.

It is well established that lymphoid dendritic cells (DC) play an important role in the immune system. Beside their role as potent inducers of primary T cell responses, DC seem to play a crucial part as major histocompatibility complex (MHC) class II+ "interdigitating cells" in the thymus during thymocyte development. Thymic DC have been implicated in tolerance induction and also by some authors in inducing major histocompatibility complex restriction of thymocytes. Most of our knowledge about thymic DC was obtained using highly invasive and manipulatory experimental protocols such as thymus reaggregation cultures, suspension cultures, thymus grafting, and bone marrow reconstitution experiments. The DC used in those studies had to go through extensive isolation procedures or were cultured with recombinant growth factors. Since the functions of DC after these in vitro manipulations have been reported to be not identical to those of DC in vivo, we intended to establish a system that would allow us to investigate DC function avoiding artificial interferences due to handling. Here we present a transgenic mouse model in which we targeted gene expression specifically to DC. Using the CD 11c promoter we expressed MHC class II I-E molecules specifically on DC of all tissues, but not on other cell types. We report that I-E expression on thymic DC is sufficient to negatively select I-E reactive CD4+ T cells, and to a less complete extent, CD8+ T cells. In contrast, it only DC expressed I-E in a class II-deficient background, positive selection of CD4+ T cells could not be observed. Thus negative, but not positive, selection events can be induced by DC in vivo.

Animals↗
PubMed1996

Redirecting the complete T cell receptor/CD3 signaling machinery towards native antigen via modified T cell receptor.

We show that a chimeric T cell receptor (TCR) beta chain consisting of a single-chain Fv portion derived from a monoclonal antibody and the full TCR beta chain is able to assemble functionally with endogenous TCR/CD3 components and transfer the antibody specificity as well as the TCR specificity into TCR beta- as well as into TCR beta+ T cells. This allows the incorporation new non-major histocompatibility complex-restricted ligand specificities into the intact TCR/CD3 complex which can exploit the full range of biological activities of the endogenous TCR signaling machinery. This approach can provide wider opportunities to redirect T cells to virus or tumor antigen-bearing cells.

Amino Acid Sequence↗
PubMed1995

Measuring and improving physician compliance with clinical practice guidelines. A controlled interventional trial.

OBJECTIVE: To determine factors that may lead physicians not to comply with clinical practice guidelines. DESIGN: Retrospective analysis of patients whose physicians were not compliant with discharge recommendations from a prospective, controlled interventional trial of a guideline to reduce hospital length of stay for patients admitted for chest pain. SETTING: A large community teaching hospital. PARTICIPANTS: Patients admitted with chest pain who were not discharged according to a practice guideline. RESULTS: 79 (34%) of 230 patients with chest pain classified as being at low risk by concurrent or retrospective review were not discharged by day 3 (the guideline recommendation). Of these 79 patients, 33 (42%) were misclassified at concurrent review (10 were falsely classified as being at high risk and 23 were falsely classified as being at low risk). Of 46 correctly classified patients, 11 (14%) were classified as having noncompliant physicians because of health care system inefficiencies. The status of 7 (9%) patients was changed to high risk between initial classification and potential discharge. For 15 patients (19%), no obvious reason for delayed discharge was found, but they had a higher severity of illness than did low-risk patients discharged according to the guideline as measured by mean time-insensitive predictive instrument scores (41.3% +/- [SD] 14.1% compared with 31.5% +/- 14.3%; P = 0.017). In 13 patients (16%), physicians refused to follow the guideline recommendations. CONCLUSIONS: In measuring and attempting to improve physician compliance with a length-of-stay guideline, physician refusal accounts for a small percentage (16%) of noncompliance. Implementation issues, health care system inefficiency, and severity of illness were the predominant reasons why physicians did not comply with guidelines. Our study further supports the principle that clinical practice guidelines should complement rather than be a substitute for physician judgment.

Chest Pain↗
PubMed1995

Total knee replacement. A guideline to reduce postoperative length of stay.

In a retrospective study in an academic, acute-care community hospital, we studied the possible safety and effectiveness of a practice guideline recommending early discharge from the hospital for patients having uncomplicated total knee replacement. Of 206 patients receiving knee replacements, 162 (79%) were classified by the guideline as being at low risk for complications between the 4th and 7th postoperative days. Use of the guideline could have reduced the postoperative length of stay from 7.3 +/- 2.6 days to 4 days for the 112 patients (54%) who became low risk on the 4th postoperative day. Explicit and implicit review of the quality of care determined that 157 patients (96.9%; 95% confidence interval, (92.9%, 99.0%) could have been safely transferred from the acute-care hospital to an appropriate setting when they became classified at low risk between the 4th and 7th postoperative days. Clinical practice guidelines can possibly be used to reduce the postoperative length of acute-care hospital stay for patients having knee replacements. This guideline requires further study in a controlled clinical trial before it can be recommended for use.

Aged↗
PubMed1994

Hip replacement and hip hemiarthroplasty surgery: potential opportunities to shorten lengths of hospital stay.

The potential safety and effectiveness of a practice guideline recommending a 5-day postoperative stay in the acute care hospital for hip surgery patients without clinical findings predictive of a complicated hospital course was studied retrospectively in 230 patients hospitalized for total hip replacement, total hip replacement with osteotomy, or hip hemiarthroplasty. Seventy percent of total hip replacement and hip hemiarthroplasty patients were classified as being at "low risk" for complications by the guideline (161 patients, or 73% of patients who remained hospitalized). Use of the guideline could have reduced the hospital length of stay from 8.4 days (standard deviation 3.3) to 5.9 days for these selected low-risk patients. Moreover, physicians' implicit review determined that 0% of patients (95% confidence interval, 0% to 2.3%) had a complication that would have benefited from continued stay in an acute care hospital after the fifth postoperative day. Our practice guideline may have the potential to safely reduce acute care hospital length of stay for patients recovering after total hip replacement and hip hemiarthroplasty. The guideline will require further study in a prospective clinical trial before it can be recommended for widespread use.

Aged↗
PubMed1994

Reducing lengths of stay in the coronary care unit with a practice guideline for patients with congestive heart failure. Insights from a controlled clinical trial.

Although more than 1,000 medical practice guidelines have been developed, there have been few evaluations of their use in clinical practice or information to judge whether practice guidelines can be used to reduce health care costs. For this reason, the authors conducted a prospective controlled clinical trial with an alternating-month design at a large teaching community hospital to study the use of a practice guideline to promote early transfer of patients admitted to a hospital with congestive heart failure (CHF) from the coronary care unit (CCU) and intermediate care unit to unmonitored beds. The practice guideline was supported by locally derived risk information and recommended consideration of early "step-down" transfer of low-risk patients with CHF 24 hours after hospital admission. Physicians caring for patients identified as "low risk" received concurrent personalized written and verbal reminders concerning the guideline recommendation. Study subjects were patients admitted to a hospital CCU and intermediate care unit between November 1, 1991 and April 30, 1993 with a diagnosis of CHF or pulmonary edema. Ninety patients with CHF were identified as low risk according to the guideline during the study period. Feedback of the practice guideline recommendation was not associated with a significant increase in physician adoption of the guideline or shorter lengths of stay in the CCU or intermediate care unit. Physicians may have compensated for statistically insignificant reductions in monitored lengths of stay by increasing the length of stay in unmonitored beds (1.80 +/- 2.32 to 4.02 +/- 4.09 days, P = .002) and the total length of stay (4.73 +/- 2.43 to 6.71 +/- 5.44 days, P = .03). Quality of patient care, patient outcomes, and patient satisfaction were not affected by the guideline. Our study results suggest that implementation of a locally derived practice guideline for patients with CHF did not result in adoption of the guideline by physicians. The complexity of implementing the guideline, changes in physician practice before the study, and the failure of the guideline to address the continuum of patient care across monitored and unmonitored beds may have accounted for rejection of the guideline. Our experience demonstrates that practice guidelines, whenever possible, should be evaluated in prospective trials before they should be disseminated for widespread use.

Adult↗
PubMed1992

Do older internists use more hospital resources than younger internists for patients hospitalized with chest pain? A study of patients hospitalized in the coronary care and intermediate care units.

OBJECTIVES: Recent concern about escalating healthcare expenditures has prompted healthcare payers and hospitals to identify physicians whose hospital resource consumption exceeds expected norms. The goals of this study were to determine whether analyses of practice patterns in this manner may a) systematically identify older physicians as big resource "spenders," and b) provide misleading information caused by the failure to adjust utilization data for severity of illness. DESIGN: A prospective, observational study. SETTING: The coronary care and intermediate care unit in an 1,100-bed community hospital. PATIENTS: A total of 217 patients hospitalized for chest pain cared for by noncardiologists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: On initial inspection, it appeared that the patients of older physicians had longer lengths of stay and greater charge expenditures than the patients of younger physicians. However, further evaluation demonstrated that older physicians cared for older (76 vs. 67 yrs old, p = .0001) and more severely ill patients (judged by risk of complications, risk of acute ischemic heart disease, and disease staging). Older physicians cared for more severely ill myocardial infarction patients than did younger physicians (Killip Classification 2.0 vs. 1.1, p less than .00003). After adjusting for severity of illness, there were fewer differences in hospital charges and consultant use between older and younger physicians, although the patients of older physicians remained hospitalized longer. CONCLUSIONS: There is little difference in resource utilization between patients cared for by older and younger internists after controlling for severity of illness. This investigation highlights the potential hazards of ignoring severity of illness when judging physician efficiency in the coronary care unit.

Age Factors↗
PubMed1989

Barriers to influenza vaccine acceptance. A survey of physicians and nurses.

The Immunization Practices Advisory Committee (ACIP) recommends that health care providers who contact high-risk patients receive influenza immunization annually. There are few available data on hospital employees' acceptance of these recommendations or their attitudes about influenza immunization. In a hospital where no formal influenza immunization program was in place, a survey of 193 nursing personnel and physicians showed that only 2.1% received the 1986-1987 trivalent influenza vaccine and 3.2% the monovalent A/Taiwan/1/86 vaccine before the 1986-1987 influenza season. An influenza-like illness developed in a total of 35.3% of hospital employees during the influenza season, and 76.6% of them cared for patients while ill. Fear of adverse reactions, avoidance of medications, and the inconvenience of vaccine administration were frequently cited reasons for declining immunization. Hospital employees would be more inclined to receive future influenza immunization if vaccine administration were more accessible and if they were informed that immunization were a national health care policy. During the influenza season, nurses and physicians should be considered a uniformly susceptible reservoir of infection capable of transmitting influenza to patients. Moreover, ACIP guidelines alone probably will not lead to acceptable immunization rates among health care providers; organized institutional efforts to promote immunization of health care providers may be required.

Attitude of Health Personnel↗
PubMed1985

Managing acute hypertension: cost considerations.

The cost-effectiveness of nifedipine for the control of acute hypertension is analyzed. The study compares routine hospital utilization of a set of patients who were administered nifedipine (the experimental group) with a set of patients who were given nitroprusside (the control group). The experimental group consists of a set of 32 patients who presented to the emergency department with acute hypertension and were treated with nifedipine. The control group is a set of 14 patients who presented with acute hypertension to the emergency departments of two other hospitals. Both experimental and control groups were seen and treated in 1983 and 1984. The patients in the control group were matched/paired with the experimental group patients. Hospital utilization was measured at four times: one, two, three, and four days after admission. For each time, utilization is classified as intensive, intermediate, or routine. In addition, intensive care is further classified according to nursing/patient ratios. Differences in both utilization levels and total costs are compared for the matched control and experimental groups.

Acute Disease↗