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Biomedical subjects

I Philip

Publications and source records attributed to I Philip.

At least 19 recordsLinked to original sources
PubMed2005

[The use of cardiac troponins (T or I) measurement in cardiology and various clinical settings].

Measurement of cardiac troponin I or T in serum (highly specific for the myocardium) have replaced classical markers, such as creatine kinase MB. Cardiac troponins are preferred markers because of their high specificity and sensitivity. This had led to modifications of the original World Health Organization criteria for acute myocardial infarction. Furthermore, the place of the troponins as superior markers of subsequent cardiac risk in acute coronary syndrome has now become firmly established, for both diagnostic and risk stratification purposes. The use of C-reactive protein and/or other inflammatory biomarkers may add independent information in this context. After non cardiac surgery, the total cardiospecificity of cardiac troponins explains why other biomarkers of necrosis should no longer be used. Recent studies suggest that any elevation of troponin in the postoperative period is indicative of increased risk of long-term cardiac complications. This prognostic value has been previously demonstrated in other clinical settings such as invasive coronary intervention (surgical myocardial revascularization and percutaneous coronary intervention) and after heart valve surgery. Increases of troponin indicate cardiac damage, whatever the mechanism (ischemic or not). Other causes of cardiac injury include: pulmonary embolism, myocarditis, pericarditis, congestive heart failure, septic shock, myocardial contusion. In most cases, elevation of troponins has been shown to be associated with a bad outcome.

Anesthesia Recovery Period↗
PubMed2005

[Recommendations for noncardiac surgery in aortic stenosis].

Aortic stenosis (AS) is the most common valve disease in western countries and its prevalence increases with population aging. AS is an important risk factor for perioperative complications in patients undergoing noncardiac surgery, a common situation in older patients. Preoperative evaluation should be based on a careful cardiac and general examination (risk factors and comorbidities) as well as on the type and urgency of the noncardiac surgery (urgent as opposed to elective). Careful teamwork and communication between the cardiologist, the anesthesiologist and the surgeon is mandatory. It is also critical that the anesthesiologist team is used to managing these high-risk patients. In cases of non-severe AS (>0.6 cm2/m2 of body surface area), the noncardiac surgery can be performed first. If AS is severe (< or =0.6 cm2/m2) and the noncardiac surgery elective, it is appropriate to consider an aortic valve replacement first. In the difficult cases of urgent noncardiac surgery in patients with severe AS, which precludes heart surgery, it is possible either to first proceed with the noncardiac surgery under very careful anesthesiologic management or to perform the percutaneous aortic valve commissurotomy first.

Aortic Valve Stenosis↗
PubMed2004

[Anesthesia of hypertensive patients].

Hypertension is a frequent condition among adults. It is one of the major risk factors of atherosclerotic diseases. Anesthetologists are frequently confronted to the management of treated or untreated hypertensive patients whose major risk during that period concerns the potential association with coronary artery disease. Therefore, the preoperative assessment should be insured of an adequate control of blood pressure, the presence of potential target organ damage and especially the detection an underlying coronary disease and its importance. The risk of cardiovascular complications and consecutively the preoperative check-up depend of the type of surgery scheduled. Preoperative systolic blood pressures (SBP) below 180 mmHg and diastolic blood pressures (DBP) below 110 mmHg are recommended. Due to their efficacy, tolerability and the easiness of their use, dihydropyridins and beta-blockers are the most frequent drugs used in the peri-operative period. Many studies evidenced the benefit of beta-blocking agents in patients with definite or potential coronary artery disease during the immediate period of major surgery, with not only a decrease of serious cardiac complications and post-operative mortality but also an improvement of mid- and longterm prognosis. There is no evidence to privilege any type of anesthesia. A respect of hemodynamic conditions (avoidance of severe hypotension and tachycardia) reduces the incidence of ischemic complications. The hemodynamic stability is obtained with an adapted anesthesia and the use of intravenous vasoconstrictive or vasodilator agents as well as beta-blockers (esmolol). The diagnosis of perioperative myocardial infarction is based on the measurement of seric concentrations of cardiac Troponin isoforms (TnI or TnT).

Anesthesia, General↗
PubMed2003

Baseline and early lymphopenia predict for the risk of febrile neutropenia after chemotherapy.

A risk model for febrile neutropenia (FN) after conventional cytotoxic chemotherapy, based on early (day 5) lymphopenia and the dose of chemotherapy, has been described. A risk index based on parameters available at day 1 would be easier in daily practice. The objectives of this work were (1) to investigate a risk model for FN using only day 1 blood cell count and (2) to compare the day 1 and day 5 risk models. Three series of patients were used for the delineation and/or validation of these two risk models: (1) the exhaustive cohort of 950 patients treated in the Department of Medicine of the CLB in 1996 (CLB-1996 series), (2) the Elypse 1 series, a prospective series of 321 patients treated in community hospitals and regional cancer centres, and (3) a previously reported Elypse 0 series of 329 patients. Day 1 blood cell count was available in all three series, while day 5 blood cell count was available only in the Elypse 0 and 1 series. In the CLB-1996 series, 92 (9.7%) patients experienced FN; only chemotherapy dose and day 1 lymphopenia < or =700 microl(-1) had an independent prognostic value for FN in multivariate analysis. In patients with both risk factors ('high-risk group'), the incidence of FN was 44, 50 and 61% in the CLB-1996. Elypse 1 and 0 series, respectively, indicating that the 'day 1' risk model enables one to identify patients at high-risk for FN. Besides, the observed incidence of FN in the high-risk group of the 'day 5' model (i.e. patients with day 5 lymphopenia < or =700 microl(-1) and receiving high-risk CT) was 45 and 69% in the Elypse 0 and 1 series, respectively. In the Elypse 1 and 0 series, 15 and 12% of all patients who experienced FN were in the high-risk group of the 'day 1' risk model as compared to 25 and 62% for the high-risk group of the 'day 5' risk model. Both day 1 and day 5 lymphopenia are associated with an increased risk of FN in patients treated with chemotherapy. The 'day 1' model identifies a small population of patients at high risk for FN, but has a lower sensitivity than the day 5 model.

Adolescent↗
PubMed2002

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients.

This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as first-line therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m(-2)) and cyclophosphamide (2 g m(-2)) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m(-2) and thiotepa 200 mg m(-2). At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m(-2) cyclophosphamide and 400 mg m(-2) thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immunosuppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity.

Adult↗
PubMed2002

Congenital bowel perforation in twin-to-twin transfusion syndrome.

Two unrelated survivors of twin-to-twin transfusion syndrome (TTTS) presented with intestinal perforation at birth. Both were localised perforations without any suggestion of widespread ischaemic disease to the splanchnic bed. Histopathology from the perforation site showed evidence of focal ischaemic necrosis, presumably from a vascular accident. One infant later died of multiple organ failure with major brain damage, but the other survived without long-term sequelae. These two cases appear to represent an unreported variation of the ischaemic intestinal complications of TTTS.

Female↗
PubMed2002

Oesophagotracheal perforation after intraoperative transoesphageal echocardiography in cardiac surgery.

Although transoesophageal echocardiography (TOE) can be considered a safe procedure, severe complications may occur. We report an oesophagotracheal perforation diagnosed 7 days after a complex and very long four-valve replacement procedure in a patient with a poor preoperative condition. We believe that an ischaemic lesion of the oesophagotracheal wall caused by the TOE probe was the initial event leading to this perforation. This observation raises concerns about the safety of prolonged TOE monitoring and suggests that a combination of risk factors (i.e. a small stature, a very long procedure, congestive heart failure, and a low cardiac output before and after cardiopulmonary bypass) may warrant increased precautions while performing TOE during cardiac surgery.

Adult↗
PubMed2002

[Necessary harmonization of health cost assessment. Autologous peripheral blood progenitor cell transplantation in France].

BACKGROUND: The purpose of this study was to determine to what extent methods used to assess health cost affect the total cost of a therapeutic procedure. METHOD: We assessed total cost of 160 consecutive therapeutic intensification procedures using autologous blood progenitor cell transplantation, 95 for lymphoma and 65 for breast tumor. RESULTS: The average total cost of the therapeutic intensification for patients with lymphoma was 227156 francs (34630 euros), including 60720 francs (9257 euros) for mobilization, 14947 francs (22402 euros) for the treatment period and 19489 francs (2971 euros) for secondary hospitalization. The average total cost for patients with a breast tumor was 199626 francs (30433 euros), including 39269 francs (5987 euros) for mobilization, 14912 francs (22737 euros) for the treatment period, and 11215 francs (1709 euros) for secondary hospitalization. CONCLUSION: We compared our findings with those from six earlier French studies. Differences in the methodologies used focuses attention on the need for incentives for better harmonization of health cost assessment.

Adult↗
PubMed2001

Utility of cardiac troponin measurement after cardiac surgery.

Postoperative cardiac failure due to myocardial necrosis remains a major complication in cardiac surgical procedures and its diagnosis is still difficult. In fact, cardiac enzymes, electrocardiogram and echographic signs are often misleading. The prognostic valve of troponin I after coronary artery bypass or conventional value surgery has been evaluated in 500 adult patients. Postoperative troponin I concentrations after cardiac surgery represent an independent variable associated with mortality (in-hospital death) and morbidity (low cardiac output and acute renal failure).

Biomarkers↗
PubMed2001

Autologous transplantation in acute myeloid leukemia: peripheral blood stem cell harvest after mobilization in steady state by granulocyte colony-stimulating factor alone.

In order to determine whether granulocyte colony-stimulating factor (G-CSF) alone initiated during steady state was able to mobilize peripheral blood stem cells (PBSC) in acute myeloid leukemia (AML) and to assess predictive factors for engraftment after autologous PBSC transplantation, we studied 49 successive adult AML patients for whom autologous transplantation was planned between July 1994 and November 1998. G-CSF was used as priming agent and was initiated at least 4 weeks after the last day of chemotherapy, while neutrophil count was >0.5 x 10(9)/l and platelet count was >30 x 10(9)/l. A median of three aphereses was performed resulting in a median collection of 14.8 x 10(8) nucleated cells/kg containing 7.7 x 10(8) mononuclear cells/kg, 47.1 x 10(4) CFU-GM/kg, and 3.8 x 10(6) CD34+ cells/kg. A significant correlation was observed between nucleated cell, mononuclear cell, and CFU-GM yields, while no correlation was found with CD34+ cell yield. Recruitment was not significantly different in patients with CD34+ leukemic cells at the time of initial diagnosis when compared to that of those presenting with CD34- blastic cells. Thirty-three patients actually underwent transplantation. Reasons for not autografting were inadequate stem cell harvest (ten patients), early relapse (two patients), prolonged neutropenia (one patient), organ failure (two patients), or patient refusal (one patient). Median time to achieve a neutrophil count greater than 0.5 x 10(9)/l and platelet count >50 x 10(9)/l untransfused was 13 and 36 days, respectively. A predictive factor for a shorter period neutropenia and a shorter thrombopenia was a higher count of harvested nucleated cells (p < 0.01 and p = 0.02, respectively). A higher count of harvested cells was also a predictive factor for less red cell and platelet transfusions (p=0.03 and p=0.02, respectively). The number of CD34+ harvested PBSC was not predictive for engraftment. We conclude that PBSC mobilization with G-CSF alone initiated in steady state is a feasible, safe, and suitable procedure for harvesting cells in sight of autologous transplantation in adult acute myeloid leukemia.

Aged↗
PubMed2001

Hyperprocalcitonemia in patients with perioperative myocardial infarction after cardiac surgery.

OBJECTIVE: To describe and compare procalcitonin (PCT) concentrations after cardiac surgery in uncomplicated patients and in patients with perioperative myocardial infarction (PMI). DESIGN: Retrospective comparative study. SETTING: One university hospital. PATIENTS: Fifty-eight adult patients undergoing cardiac surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In a first step, plasma PCT and C-reactive protein concentrations were measured preoperatively and until 72 hrs postoperatively in ten consecutive patients who underwent uncomplicated cardiac surgery. PCT concentrations increased progressively from the end of cardiopulmonary bypass (0.09 +/- 0.09 ng/mL), peaked at 24 hrs postoperatively (1.14 +/- 1.24 ng/mL), and began to decrease at 48 hrs. C-reactive protein appeared to peak at 48 hrs (from 5.8 +/- 11.7 mg/L preoperatively to 265.1 +/- 103.5 mg/L on the second postoperative day). In a second step, PCT concentrations were measured at day one in 23 patients (PMI group) who presented high postoperative plasma cardiac troponin I concentrations and were compared with PCT concentrations observed in 25 matched uncomplicated patients. All patients were free from infection. PCT in the PMI group was significantly higher than in the control group (27.1 +/- 63.2 vs. 2.0 +/- 2.4 ng/mL, respectively; p =.0053). CONCLUSION: Because high plasma concentrations of PCT were found in patients with PMI after cardiac surgery, it may be suggested that, in the early postoperative period, elevated plasma PCT concentrations should be interpreted with caution regarding infection diagnosis.

Adult↗
PubMed2000

Research controversies in management of oral mucositis.

The management of mucositis is the subject of many controversies, and the optimal treatment is still not known. Several evaluation scoring systems have been described, but no one of these is appropriate to all clinical situations: a simple scale such as that devised by the WHO can be used routinely, and more sophisticated ones can be implemented by trained experimenters working in research. We have considered the impact of each of the treatments currently available on each stage of mucositis. In attempts at prevention, self-care, in the sense of oral hygiene, must remain atraumatic. It is probably advisable to differentiate patients with good previous oral care, in whom tooth brushing is beneficial, from others, in whom the risk of hemorrhage and infection excludes any brushing. Before the dosage of chemotherapy is reduced, the curative or palliative intent of the strategy must be carefully evaluated. In the vascular phase protection of the proliferating cells is attempted by means of vasoconstriction (cryotherapy), cytoprotection (prostaglandin E2 and other antioxidants) or epithelial cell-inhibiting factors such as TGF-B3. Treatments applied in the epithelial phase are directed at increasing the cell proliferation to accelerate epithelial restoration by sucralfate and several growth factors: hematopoietic GF, which has demonstrated a direct effect on the mucosa (GM-CSF), or epithelial growth factors such as keratinocyte GF. In the ulcerative and bacteriological phase attempts are made to attenuate sepsis by means of antiseptics (chlorhexidine), amphotericin B and antiviral agents or antibiotic lozenges. In the healing phase application of the low-energy helium-neon laser has demonstrably been followed by a later time of onset, less pronounced peak severity and shorter duration of oral mucositis. After cancer treatment, oral hygiene, inhibition of oral flora, and pain relief are the main goals. Physiopathogen-specific treatment is the next step, with the emphasis on the inhibition of epithelial cell proliferation during drug exposure and facilitation of epithelial maturation and healing.

Antineoplastic Agents↗
PubMed2000

Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution.

OBJECTIVE: The aims of our study performed in myeloma were to evaluate the performance and the safety of Systemix's high-speed clinical cell sorter, to assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+ hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment, and to assess the residual tumor cell contamination using polymerase chain reaction (PCR) amplification assays of patient-specific complementarity determining region III (CDR III) analysis for residual myeloma cells. MATERIALS AND METHODS: The clinical trial was performed in 31 multiple myeloma patients, using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de-escalation/escalation design. RESULTS: Twenty-three patients were transplanted. Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above the threshold dose of 0.8 x 10(6) CD34+Thy1+ HSCs/ kg provided prompt engraftment (absolute neutrophil count >0.5 x 10(9)/L day 10; platelet count >50 x 10(9)/L day 13). A higher rate of infections was observed in the early and late follow-up phases than usually reported after CD34+ selected or unselected autologous transplantation, which did not correlate with the CD34+Thy1+ HSC dose infused. Successful PCR for CDR III could only be performed in five patients on initial apheresis product and final CD34+Thy1+ HSC product and showed a median tumor log reduction >3.12. CONCLUSIONS: CD34+Thy1+ HSCs are markedly depleted or free of detectable tumor cells in multiple myeloma and are capable of producing fast and durable hematopoietic reconstitution at cell doses >0.8 x 10(6) CD34+Thy1+ HSCs/kg. The delayed immune reconstitution observed is not different from that described in unselected autologous bone marrow and peripheral blood mononucleated cells transplants in multiple myeloma and may be corrected by addition of T cells either to the graft or to the patient in the posttransplant phase.

Adult↗
PubMed2000

Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-alpha.

In chronic myelogenous leukemia (CML), autologous stem cell transplantation could be a promising new approach for patients with no cytogenetic response after interferon alpha (IFN-alpha) therapy. We report data on 28 CML patients autotransplanted in chronic phase with peripheral blood progenitor cells mobilized with G-CSF (5 microg/kg/day x 5 days) given subcutaneously while continuing IFN-alpha therapy. At mobilization, 23 patients (82%) were in complete hematological remission (CHR), 16 (57%) achieved a minor cytogenetic response (mcr). We obtained, after stimulation, a median of 37.4 x 10(9)/l (6.9-108) white blood cells, 7.2 x 10(8)/kg (2.2-16.6) mononuclear cells, 39 x 10(4)/kg (4.8-403.5) CFU-GM and 4.2 x 10(6)/kg (0-58.6) CD34+ cells. Six patients received GM-CSF after transplantation. All patients engrafted, with no significant influence stemming from the Sokal index score and pretransplantation IFN-alpha therapy duration. The first cytogenetic evaluation after transplantation showed 11 (39%) major cytogenetic response (Mcr), and nine (32%) mcr with no significant correlation between these responses, the Sokal index score, and pretransplantation IFN-alpha therapy duration, although there was a significant impact from GM-CSF administration (P=0.01). After transplantation, 26 patients received IFN-alpha alone or associated with hydroxyurea. The median follow-up was 12 months after transplantation and 57 months after diagnosis. At the time of follow-up, nine patients were in CHR, six remained stable in chronic phase, three presented an mcr and one remained in Mcr. At the last follow-up, 22 patients were alive. We conclude that the results of this strategy are encouraging in poor IFN-alpha responders but that other prospective studies that try to maintain the cytogenetic responses obtained immediately after transplantation are needed.

Adult↗
PubMed2000

Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells: roles of interleukin-10 and the extracorporeal circuit.

OBJECTIVE: To determine whether cardiopulmonary bypass (CPB) alters the ex vivo cytokine production of whole blood cells stimulated by lipopolysaccharide (LPS) and to assess the roles of interleukin (IL)-10 and an extracorporeal circuit (ECC) in the alteration. DESIGN: Prospective, controlled study. SETTING: Biochemistry laboratory and surgical intensive care unit in a university hospital. PATIENTS: Seventeen consecutive adult patients undergoing coronary artery bypass grafting or valve surgery with normothermic CPB and eight healthy volunteers. INTERVENTIONS: Blood samples for cytokine measurement were drawn from patients before and during (at 60, 90, 120, 180 and 360 mins) CPB and were cultured with and without LPS and with and without anti-IL-10 antibodies. Blood was also drawn from healthy subjects and sampled for cytokine analysis before and during circulation in an isolated ECC. MEASUREMENTS AND MAIN RESULTS: The concentrations of ex vivo tumor necrosis factor (TNF)-alpha, IL-6, IL-8, and IL-10, measured by enzyme-linked immunosorbent assay, were reduced in both experimental settings. In patients on CPB, LPS hyporesponsiveness was detected at 60 mins after the onset of CPB and was maximal at 120 mins (78% to 86% decreases from pre-CPB levels) but was transient, except for TNF-alpha. The plasma concentration of IL-10 peaked at 90 mins after the start of CPB, but the role of IL-10 in LPS hyporesponsiveness appears limited because anti-IL-10 antibodies significantly increased ex vivo production of IL-6 but not TNF-alpha or IL-8. In the isolated ECC study, no IL-10 was detected in plasma, yet the ex vivo production of the cytokines (except IL-8) was decreased (by 66% to 95%). CONCLUSION: Our results demonstrate the following: a) CPB induces an early and transient LPS hyporesponsiveness of whole blood as measured by cytokine production; b) IL-10 seems only partly involved in this process, and its role is restricted to an in vivo situation; and c) contact of blood with an ECC is sufficient to induce LPS hyporesponsiveness.

Blood Cells↗
PubMed2000

[Partial tricuspid homograft: a new technique for tricuspid valve repair. Report of a case].

The authors report the case of a drug abuser treated successfully for fungal tricuspid endocarditis complicated by massive pulmonary embolism. Partial valvular replacement with a segment of a tricuspid homograft associated with disobliteration of a pulmonary artery was performed. Peroperative transoesophageal echocardiography showed satisfactory tricuspid valve function. The postoperative course was uneventful. After 5 months' follow-up, the patient was asymptomatic and in good general condition. Control echocardiography showed a stable operative result.

Adult↗
PubMed1999

Cryptic exons as a source of increased diversity of Ewing tumor-associated EWS-FLI1 chimeric products.

In the Ewing family of tumors (EFT), the EWS gene is rearranged with members of the ets oncogene family. Variability in genomic breakpoint locations is the source of significant heterogeneity in fusion product structure. As a consequence of variably included exon sequences from the two partner genes, a variable amount of additional peptide sequence is inserted in between the minimal transforming domains. Some of this molecular diversity has recently been correlated with disparate clinical outcome. Here we report on cryptic exons found in the chimeric RNA of three EFT with different EWS-FLI1 fusions. In two tumors, the emergence of a cryptic exon from FLI1 intron 5 in the chimeric RNA was apparently unrelated to the genomic rearrangement that occurred in FLI1 introns 4 and 5, respectively. In one case, a novel exon was generated through the creation of an artificial splice acceptor site in FLI1 intron 6 by the genomic rearrangement that occurred in EWS intron 8. These results further extend the spectrum of molecular diversity in EFT.

Adolescent↗