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Biomedical subjects

F Lefevre

Publications and source records attributed to F Lefevre.

At least 37 records · Page 2Linked to original sources
PubMed1998

Lymphoproliferative disorders after renal transplantation: role of medical imaging.

Post-transplantation lymphoproliferative disorders (PTLD) are a complication of immunosuppressed transplant recipients, and their incidence is reported to be 20-120 times greater than the rate in the general population. After kidney transplantation, PTLD more likely arise within the renal transplant fossa. Radiological patterns of these forms are presented and discussed, according to a review of the literature, and illustrated by cases from our institution. Ultrasound plays an essential role in the early diagnosis of PTLD by detecting a urinary obstruction associated with adenopathy or an ill-defined mass not previously seen. However, in the case of an inconclusive US examination, CT or MRI should be performed to confirm the presence of a mass. Both techniques are useful in evaluating the extension of the process within the transplantation fossa; MRI seems more accurate and can be used for the follow-up, especially after reduction in immunosuppressive therapy without transplant removal.

Biopsy↗
PubMed1997

Systolic function, readmission rates, and survival among consecutively hospitalized patients with congestive heart failure.

We sought to describe the relation between left ventricular systolic function and rates of hospital readmission and survival among consecutively hospitalized patients with congestive heart failure. Medical records were reviewed for these patients at an academic medical center between Jan. 1, 1992, and Dec. 31, 1993. Left ventricular systolic function assessments performed within 6 months before discharge were used to classify left ventricular systolic function. Hospital readmission rates and survival through Dec. 31, 1994, were compared between patients with systolic dysfunction and those with preserved systolic function. Among 412 patients hospitalized with a primary diagnosis of congestive heart failure, 224 had undergone a left ventricular function assessment during the 6 months before hospital discharge. In-hospital mortality and readmission rates were higher among patients without a recent assessment of left ventricular systolic function. Of patients with systolic dysfunction, 55% versus 41% of patients with preserved systolic function were either readmitted or had an emergency room visit within 6 months after discharge (p = 0.06). At 27 months' follow-up, cumulative survival probabilities were 65% for patients with preserved systolic function, 65% for patients with systolic dysfunction, and 60% for patients without a left ventricular systolic function assessment (p = 0.24). Patients without a recent left ventricular systolic function assessment have significantly higher hospital readmission rates than patients with a recent systolic function assessment. Among hospitalized patients, mortality rates are comparable between patients with systolic dysfunction and those with preserved systolic function. However, patients with heart failure with systolic dysfunction may have higher readmission rates.

Aged↗
PubMed1997

Heart failure between 1986 and 1994: temporal trends in drug-prescribing practices, hospital readmissions, and survival at an academic medical center.

Since 1987, publications in widely circulated medical journals have reported improved survival and lower hospital readmission rates when patients with heart failure and systolic dysfunction are treated with angiotensin-converting enzyme (ACE) inhibitors. We describe changes in ACE inhibitor use among patients hospitalized with heart failure between 1986 and 1993. Simultaneous trends in readmissions and survival rates are reported. Subjects were 612 consecutive patients hospitalized with a principal diagnosis of heart failure at an academic medical center during the period of Sept. 1, 1986, to Dec. 31, 1987 (interval I) or during the period Aug. 1, 1992, to Nov. 30, 1993 (interval II). Medical records were reviewed for 434 patients, consisting of all patients hospitalized with heart failure during interval II and a randomly selected 50% subset of patients hospitalized during interval I. Among 145 patients with systolic dysfunction whose medical records were reviewed, ACE inhibitor prescriptions significantly increased between interval I and interval II (43% vs 71%, p < 0.01, odds ratio 3.22, 95% confidence interval 1.62 to 6.42). Prescriptions of ACE inhibitors combined with digoxin and a diuretic also increased (37% vs 56%, p = 0.02, odds ratio 2.22, 95% confidence interval 1.14 to 4.32). Among all 612 patients, 6-month heart failure readmission rates increased from 13% to 21% (p = 0.02, odds ratio 1.79, 95% confidence interval 1.10 to 2.82). There was no significant change in survival rate between interval I and interval II, however, survival rate was marginally significantly improved among patients with systolic dysfunction. Our results suggest that drug-prescribing practices have significantly changed between 1986 and 1993. The absence of observed improvement in outcomes may result from changes in hospital admission criteria for heart failure.

Aged↗
PubMed1997

A new Object Request Broker architecture in implementing a medical picture retrieval system.

This paper describes the approach we used to implement the world wide web user interface of MediPict, a medical picture retrieval system. The best software architecture seemed to be the three-tier client/server architecture using Objects Request Brokers (ORB) which appears to have many benefits. Although CORBA appears to be the standard ORB, we found it more adequate to develop a different approach. This new ORB resolves many of CORBA's weaknesses (non coherent types, need of a static IDL, maintenance difficulties) by using the same language on the top and middleware tiers.

Computer Communication Networks↗
PubMed1995

Atypical porcine type I interferon. Biochemical and biological characterization of the recombinant protein expressed in insect cells.

A recombinant baculovirus was designed to express short porcine type I interferon (spI interferon), a novel and atypical type I interferon that was recently described as the product of a gene transcribed in pig trophoblast at the time of implantation in the uterus [Lefèvre, F. & Boulay, V.C. (1993) J. Biol. Chem. 268, 19,760-19,768]. The recombinant protein, secreted into the culture medium of Sf9 cells at 3 days post infection (60,000 IU/ml), was purified by ion-exchange and reverse-phase HPLC. N-terminal sequencing confirmed the predicted signal peptide cleavage site and therefore the size of the mature protein (149 amino acids), the shortest of all reported type I interferons. Purified spI interferon, with a specific antiviral activity using Madin-Darby bovine kidney cells of 3.7 x 10(7) IU/mg, is an N-glycosylated monomer of 19 kDa that possesses several physicochemical characteristics of interferons: (a) disulfide bonds are necessary for bioactivity; spI interferon is thermolabile, stable at pH 2, and able to renature after complete denaturation (1% 2-mercaptoethanol, 1% SDS, and 5 M urea); (b) the carbohydrate chain is not essential for bioactivity since no loss of antiviral activity is observed following complete deglycosylation. In this study, antiviral and anti-proliferation activities of spI interferon in cell culture were compared with those of other interferons, especially with porcine type 1 interferon-alpha. A major difference with porcine type 1 interferon-alpha was that spI interferon was not active on human cells in either test, and it was relatively more active on pig cells compared to bovine cells than porcine type 1 interferon-alpha. Serological cross-neutralization results obtained with anti-(spI interferon) serum confirmed that several members of interferon families are not antigenically related to spI interferon, in agreement with previous observations; this provides further evidence that spI interferon could represent a new family of type I interferon.

Amino Acid Sequence↗
PubMed1995

Changes in study design, gender issues, and other characteristics of clinical research published in three major medical journals from 1971 to 1991.

OBJECTIVE: To examine trends in study design and other characteristics of original research published in JAMA, Lancet, and the New England Journal of Medicine (NEJM) between 1971 and 1991. DESIGN: A retrospective cross-sectional study of original clinical research published in JAMA, Lancet, and NEJM during 1971, 1981, and 1991. MEASUREMENTS: Four hundred forty-four articles were independently reviewed by at least two investigators and classified according to study design and other preselected study characteristics. Changes over time were analyzed by chi-square tests for categorical variables and analysis of variance for continuous variables. MAIN RESULTS: Clinical results doubled, from 17% of all articles in 1971 to 35% in 1991 (p < 0.004), while case series decreased from 30% to 4% (p < 0.0001). Of 118 clinical trials, randomized controlled trials increased from 31% to 76% (p < 0.003) and nonrandomized controlled trials decreased from 42% to 8% (p < 0.002). Multicenter studies increased from 10% to 39% (p < 0.0001) and the prevalence of health services research increased from none in 1971 to 12% in 1991 (p < 0.001). The proportion of the studies explicitly excluding women from the subject population decreased from 11% in 1971 to 3% in 1991 (p < 0.03). In 1991 7% of the studies were composed entirely of men subjects, while only 0.7% of the studies were specific to men's health. Twelve percent of the studies in 1991 were specific to women's health. Between 1971 and 1991 there was no change in the prevalence of women first authors or studies addressing women's or minorities' health issues. CONCLUSIONS: Several important changes in clinical research studies published in JAMA, Lancet, and NEJM have taken place between 1971 and 1991. Clinical trials have increased in frequency, largely replacing studies containing ten or fewer subjects. Health services research has increased in prevalence, reflecting growing interest in studies addressing the delivery of health care. Our data support the hypothesis that exclusion of women from clinical research studies is an important contributor to the paucity of data concerning women's health.

Clinical Trials as Topic↗
PubMed1995

Alcohol consumption among HIV-infected patients.

This prospective, cohort study analyzed the prevalence of alcoholism and patterns of alcohol intake over time in a cohort of HIV-infected patients, predominantly homosexual/bisexual men. One hundred eleven HIV-positive subjects were recruited from a comprehensive HIV clinic associated with a large Midwestern university hospital. Each participant completed the Michigan Alcoholism Screening Test (MAST) survey and a standardized quantity-frequency questionnaire on alcohol intake at enrollment. The quantity-frequency scale was repeated every six months for a total of 30 months. Forty-five of the 111 subjects (41%) met the criteria for alcoholism, as defined by a MAST score 5 or higher. There was a significant decrease in alcohol consumption over time, from 6.4 drinks/week in the initial time period to 3.9 drinks/week by the final time period (p < 0.001).

Alcohol Drinking↗
PubMed1995

Atypical spI interferon binds on porcine cells to a major component of type I interferon receptor.

The short porcine type I interferon (spI IFN), encoded by a gene physiologically expressed by the pig embryonic trophoblast during implantation, represents the first member of a novel family type I IFN. Binding and cross-linking experiments were carried out to characterize its cellular receptor. On porcine kidney cells, specific binding of 125I-spI IFN could be displaced significantly by spI IFN, rpIFN-alpha 1, and rhIFN-alpha 1, but not by rhIFN-alpha 2a or by rpIFN-gamma. On the other hand, all these type I IFNs but not rpIFN-gamma were capable of displacing bound 32P-hIFN-alpha A-P1 on these cells. Cross-linking data show that the specific 120 kD complex formed with these two radiolabeled ligands was displaceable by an excess of both spI IFN and rpIFN-alpha 1. These results provide primary evidence that spI IFN shares at least the major binding subunit of type I IFN receptor on porcine cells. On human WISH cells, 125I-spI IFN did not form any complex, nor did spI IFN affect cross-linking complexes of 32P-hIFN-alpha A-P1 on these cells, unlike rpIFN-alpha 1. The lack of antiviral and antiproliferative effects of spI IFN on human cells is primarily a result of its inability to recognize human type I IFN receptor.

Animals↗
PubMed1995

A GTP-binding protein modulates a Ca2+ pump present in reticulocyte endocytic vesicles.

Rat reticulocytes were used to prepare endocytic vesicles to study calcium fluxes across the endosomal membrane. We used 45Ca2+, and found that endocytic vesicles from reticulocytes present a Ca(2+)-ATPase that pumps Ca2+ into the lumen of vesicles. This activity was sensitive to vanadate and the calmodulin antagonists: trifluoperazine and calmidazolium. Western blot analysis using a monoclonal antibody evidenced that Ca(2+)-ATPase present in reticulocyte endocytic vesicles is probably the same as the erythrocyte Ca2+ pump. Ca2+ pump activity was shown to be partially inhibited by GTP gamma S. Moreover, mastoparan and benzalkonium chloride, both activators of heterotrimeric G proteins, were found to decrease 45Ca2+ uptake by endocytic vesicles. These results suggest the involvement of a trimeric G protein in the modulation of Ca(2+)-ATPase.

Animals↗
PubMed1994

ST segment depression detected by continuous electrocardiography in patients with acute ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Forty percent of patients with a history of ischemic stroke or transient ischemic attack (TIA) have concomitant coronary artery disease. ST segment depression, detected by continuous electrocardiography, is associated with increased cardiac morbidity and mortality in patients with known coronary artery disease. While electrocardiographic changes have been associated with acute stroke, the etiology and significance of these changes remain unclear. In this pilot study we report the prevalence of ST segment depression and ventricular arrhythmias in patients with acute ischemic stroke or TIA monitored by continuous electrocardiography. Clinical predictors of ST segment depression and ventricular arrhythmia are also identified. METHODS: Consecutive patients presenting with acute ischemic stroke or TIA were enrolled within 72 hours of hospital admission and monitored by continuous electrocardiography for 48 hours. The electrocardiographic results were analyzed for periods of ST segment depression and ventricular arrhythmias. RESULTS: Of 51 patients with ischemic stroke or TIA, 15 (29%) had episodes of ST segment depression (95% confidence interval, 15% to 43%), and 18 (35%) had ventricular arrhythmias (95% confidence interval, 21% to 49%). In logistic regression analysis, increasing age (P < .02) and a left-sided neurological event (P < .01) were significant predictors of ST segment depression. Increasing numbers of atherosclerotic risk factors, a history of cardiac disease, and increasing or decreasing mean arterial pressure were not predictive of ST segment depression. CONCLUSIONS: Patients with acute ischemic stroke or TIA have a 29% prevalence of ST segment depression within the first 5 days after their event. In comparison, the prevalence of ST depression is 2.5% to 8% in asymptomatic adults and 43% to 60% in patients with symptomatic coronary artery disease. The association of ST segment depression with left-sided neurological events suggests that the electrocardiographic changes are in part neurologically mediated. Further study is necessary to better define the brain-heart interaction and to determine whether ST segment depression in patients with ischemic stroke or TIA reflects underlying coronary artery disease.

Acute Disease↗
PubMed1993

Predicting survival from in-hospital CPR: meta-analysis and validation of a prediction model.

OBJECTIVE: To better clarify patient factors that predict survival from in-hospital cardiopulmonary resuscitation (CPR), using two methods: 1) meta-analysis and 2) validation of a prediction model, the pre-arrest morbidity (PAM) index. DESIGN: Meta-analysis of previously published studies by standard techniques. Retrospective chart review of validation sample. SETTING: University-affiliated teaching hospital. PATIENTS/PARTICIPANTS: Meta-analytic sample of 21 previous studies from 1965-1989. The validation sample consisted of all patients surviving resuscitation from the authors' hospital during the period September 1986 to January 1991. A matched sample of patients who did not survive from the same time period was used as the comparison group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The strongest negative predictors of survival, by meta-analysis, were renal failure (r = 0.088, p < 0.0002), cancer (r = 0.08, p < 0.0002), and age more than 60 years (r = 0.063, p < 0.006). Sepsis (r = 0.046, p < 0.02), recent cerebrovascular accident (CVA) (r = 0.038, p < 0.04), and congestive heart failure (CHF) class III/IV (r = 0.036, p < 0.05) were weaker negative predictors. Presence of acute myocardial infarction (AMI) was a significant positive predictor of survival (r = 0.15, p < 0.0001). The PAM score was highly predictive of survival in a logistic regression model (p < 0.0003, R2 = 9.6%). No patient who survived to discharge had a PAM score higher than 8. CONCLUSION: Meta-analysis reveals that the most significant negative predictors of survival from CPR are renal failure, cancer, and age more than 60 years, while AMI is a significant positive predictor. The PAM index is a useful method of stratifying probability of survival from CPR, especially for those patients with high PAM scores, who have essentially no chance of survival.

Age Factors↗
PubMed1993

Use of the Rand Structured Implicit Review Instrument for Quality of Care Assessment.

The Rand Structured Implicit Review Instrument is a 27-item instrument that rates process quality of care for patients with five common illnesses. This study reports on the use of this instrument for hospitalized patients with long lengths of stay. A total of 120 medical records were reviewed by multiple physician reviewers for patients discharged with congestive heart failure, acute myocardial infarction, and pneumonia. Mean inter-rater reliability was assessed for a subsample of six records by kappa score. A multiple regression analysis was used to estimate the relationship between process ratings for the quality of documentation, assessment, monitoring, and therapy and overall quality of care scores, controlled for physician judgments about patients' prognosis and selected patient characteristics. Each reviewer also evaluated the instrument. Mean kappa for trichotomized ratings of quality of care was 0.50. The majority of all quality of care ratings were in the good or very good range (77.5%). The full regression model, including process subscale quality ratings, prognostic items, and patient characteristics, accounted for 38% of the total variance in the quality of care ratings. Items measuring the quality of assessment (p < 0.0001), therapy (p < 0.02) and monitoring (p < 0.01) were significant. Physicians accepted the use of such a form moderately well. The Rand quality of care form shows consistency in rating overall quality of care and individual dimensions of quality. Achieving a high level of inter-rater reliability is difficult with implicit review. By focusing on specific areas of potentially deficient care, structured review instruments can improve clinical quality improvement efforts.

Humans↗
PubMed1992

Iatrogenic complications in high-risk, elderly patients.

BACKGROUND: This study explores the quality improvement potential of reviewing care for long-stay, elderly medicine service patients hospitalized for congestive heart failure, acute myocardial infarction, or pneumonia at a large Midwestern teaching hospital. METHODS: Medical records were reviewed for 120 patients aged 65 years or older who were discharged between January 1987 and June 1989, with hospital stays of 15 days or longer. Patients' severity of illness on admission was rated using the Medicare Mortality Predictor System; process quality of care was rated using a structured implicit review form for judging several dimensions of clinical assessment and decision making. Serious complications were coded by etiology and type and judged as possibly or probably preventable. Logistic regression was used to identify risk factors for iatrogenic events; multiple regression was used to assess potential outcome bias in ratings of overall quality of care. RESULTS: Of 120 medical records reviewed, 70 (58.3%) suffered at least one iatrogenic complication. Forty-three patients (35.8%) suffered an iatrogenic complication rated as potentially preventable. Significant predictors of all iatrogenic complications were quality ratings of initial physician assessment, patients' inability to walk unassisted, and low Glasgow Coma Score. For potentially preventable complications, quality ratings for physician documentation of functional status were also significant. Ratings for overall quality of care were not significantly influenced by the mere presence of death or complications. CONCLUSIONS: Iatrogenic complications are likely to be an extremely common experience for elderly medicine service patients with long lengths of stay. A significant portion of these complications may be potentially preventable with closer attention to initial assessment and documentation of patients' functional status.

Aged↗
PubMed1991

Production of an hybridoma library to recombinant porcine alpha I interferon: a very sensitive assay (ISBBA) allows the detection of a large number of clones.

The preparation of a panel of hybridoma cell lines secreting monoclonal antibodies (MAbs) specific for Recombinant Porcine Alpha I Interferon is reported. Of these MAbs, 28 were subcloned and 21 secreted their antibody during several months. They were partially characterized for their ability to bind and neutralize Alpha Interferons (IFNs-alpha) from different animal species. All the clones bound Recombinant Porcine IFN-alpha 1, 8 bound Human leukocyte IFN, and one bound recombinant Human IFN-alpha 2b, but not IFN-alpha 2a. Two screening procedures were used for the detection of specific MAbs: neutralization assay and immunosorbent binding bioassay. This last method appears to be simple and very sensitive since it permits to detect 100 pg/ml MAb. In addition it can detect weakly, as well as strongly neutralizing antibodies. Probable mechanisms involved in this assay, and possible applications of this method for IFNs-alpha subtyping are discussed.

Animals↗
PubMed1991

The porcine family of interferon-omega: cloning, structural analysis, and functional studies of five related genes.

We report the molecular characterization of the porcine IFN-omega multigenic family which appears to comprise six to seven loci. Five of these loci were cloned and sequenced, revealing two pseudogenes (psi PoIFN-omega 1 and -omega 2) and three genes with an intact reading frame (PoIFN-omega 3, -omega 4, and -omega 5) that could encode preproteins of 179-190 amino acids including a putative signal peptide of 23 residues. By comparison of porcine IFN-omega coding sequences to those of known mammalian counterparts, it appeared that porcine sequences contain an in-frame five-codon deletion (between positions 113 and 117) in a region of relatively high sequence variability. In vitro transcription and translation of the three potentially functional reading frames gave rise to proteins with antiviral activity, showing that the porcine-specific deletion does not abolish the biological activity. Comparative analysis of flanking sequences revealed unique features of the 3' untranslated region of IFN-omega 4 gene: It contained a consensus estrogen-responsive element (ERE) in the vicinity of an extensive A-T-rich sequence known to serve a specific regulatory role in the expression of many genes involved in the inflammatory response. This finding suggests that the expression of the functional members of the porcine IFN-omega family may be mediated through different mechanisms. The expression of these genes was studied by Northern blot analysis of mRNAs from pig conceptus (days 14-20). Five bands of poly(A)+ RNAs hybridized with an IFN-omega probe provided the stringency was low, suggesting that a distinct family of IFN-omega-related genes were expressed by porcine trophoblastic cells during early gestation.

Amino Acid Sequence↗
PubMed1986

Molecular cloning and sequencing of a gene encoding biologically active porcine alpha-interferon.

Nine distinct genomic clones containing human alpha 1-interferon (IFN-alpha 1) related sequences were isolated from a porcine genomic library constructed in phage lambda. Restriction mapping and Southern blot analysis revealed that these clones contained a total of 10 potential porcine IFN-alpha genes or pseudogenes belonging to a multigene family of at least 12 members. One of these genes was subcloned in plasmid pUC8 and the recombinant plasmid obtained was shown to direct the synthesis of a low but detectable IFN-alpha activity in Escherichia coli JM103. The sequence of this porcine IFN-alpha gene (Po IFN-alpha 1) was determined. As expected, it contained no introns and encoded a 189-amino-acid-long preprotein with a putative signal peptide of 23 residues. The homology to human (Hu)IFN-alpha 1 was 78.5% at the nucleotide level and 64% at the amino acid level.

Amino Acid Sequence↗