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Biomedical subjects

I Philip

Publications and source records attributed to I Philip.

At least 37 records · Page 2Linked to original sources
PubMed1999

G894T polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine.

BACKGROUND: Differences in vascular reactivity to phenylephrine (PE) responsiveness have been largely evidenced in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Because nitric oxide (NO) strongly affects modulation of the vascular tone in response to vasopressor agents, we hypothesized that the G894T polymorphism of the endothelial NO synthase gene (eNOS) could be related to changes in the pressor response to PE. METHODS AND RESULTS: The protocol was performed in 68 patients undergoing coronary artery bypass grafting (n=33) or valve surgery (n=35) in whom mean arterial pressure decreased below 65 mm Hg during normothermic CPB. Under constant and nonpulsatile pump flow conditions (2 to 2.4 L. min-1. m-2), a PE dose-response curve was generated by the cumulative injection of individual doses of PE (25 to 500 micrograms). The G894T polymorphism of the eNOS gene was determined, and 3 groups were defined according to genotype (TT, GT, and GG). Groups were similar with regard to perioperative characteristics. The PE dose-dependent response was significantly higher in the allele 894T carriers (TT and GT) than in the homozygote GG group (P=0.02), independently of possible confounding variables. CONCLUSIONS: These results evidenced an enhanced responsiveness to alpha-adrenergic stimulation in patients with the 894T allele in the eNOS gene.

Adrenergic alpha-Agonists↗
PubMed1999

Congenital giant prepucial sac: case reports.

The normal attachment of the prepuce is at the coronal sulcus of the penis. In this report, the authors describe an abnormal attachment of the prepucial skin, leading to a giant, deep prepucial sac. This acted as a stagnant sump for urine, and was cured by modified circumcision.

Circumcision, Male↗
PubMed1999

The deletion genotype of the angiotensin I-converting enzyme is associated with an increased vascular reactivity in vivo and in vitro.

OBJECTIVES: To define a link between the deletion genotype (DD) and vascular reactivity, we studied in vivo and in vitro phenylephrine (PE)-induced tone and the effect of angiotensin II (AII) at physiological (subthreshold) concentrations on PE-induced tone. BACKGROUND: The deletion allele (D) of the angiotensin I-converting enzyme (ACE) has been associated with a higher circulating and cellular ACE activity and possibly with some cardiovascular diseases. METHODS: During cardiac surgery PE-induced contraction was studied in patients with excessive hypotension. In parallel, excess material of internal mammary artery, isolated from patients operated for bypass surgery, was mounted in an organ chamber, in vitro, for isometric vascular wall force measurement. RESULTS: In patients under extracorporeal circulation, PE (25 to 150 microg) induced higher contractions in patients with the DD genotype (e.g., with PE 75 microg: 20.3 +/- 2.9 vs. 11.5 +/- 2.5 mm Hg/ml per min, DD vs. II/ID, n = 15 vs. 30, p < 0.03). In the mammary artery, in vitro, contractions to PE (0.1 to 100 micromol/liter) or AII (1 or 100 nmol/liter) were not affected by the genotype. Angiotensin II (10 pmol/liter) significantly potentiated PE (1 micromol/liter)-induced contraction in both groups. Potentiation of PE-induced tone by AII was significantly higher in the DD than in the II/ID group. CONCLUSIONS: The DD genotype was associated with an increased reactivity to PE in vivo and potentiating effect of exogenous AII in vitro. The higher response to PE in vivo might reflect a higher potentiation by endogenous AII. These data should be considered to understand possible link(s) between cardiovascular disorders and the ACE gene polymorphism.

Aged↗
PubMed1999

[High dose chemotherapy with autologous stem cell support in the treatment of germ cell tumors: experience of the centre Léon-Bérard between 1982 and 1996].

More than 80% patients with metastatic germ cell tumors are cured by chemotherapy and surgery. Since 1980, intensive chemotherapy with autologous bone marrow was developed for the patients who where not cured by conventional chemotherapy. We present the experience of the Centre Léon-Bérard, between 1982 and 1996, seventy-five metastatic germ cell tumors patients were treated with high dose chemotherapy and autologous stem cell support. Forty-six patients received cisplatin, etoposide, ifosfamide (VIC regimen), 17 carboplatin, etoposide, cyclophosphamide (CarboPEC regimen), 9 cisplatin, etoposide, cyclophosphamide (PEC) and 10 had another regimen. The chemotherapy was administred in different situations: 31 patients with poor prognosis in first line, 15 in salvage of sensitive relapse, 15 in salvage of incomplete response, and 14 with a cisplatin refractory disease. The complete response rate was 31% among the 54 evaluable patients. Seven patients died as a consequence of the treatment. The two-year overall actuarial survival and the event free survival were respectively 67% and 57% (median 42 months). Only 2 patients who had a refractory disease are continuously disease-free at 42 and 87 months after regimen. The renal toxicity was more severe with regimen VIC than with CarboPEC 30% versus 60%, whereas the hematologic toxicity are similar with both. This study shows the feasability of high dose chemotherapy. Two refractory patients are alive, and the results seem to be interesting for the patients in salvage treatment. But this treatment is not a standard for germinal cell tumors and randomized trials are ongoing.

Adolescent↗
PubMed1998

Elevated levels of 8-iso-prostaglandin F2alpha in pericardial fluid of patients with heart failure: a potential role for in vivo oxidant stress in ventricular dilatation and progression to heart failure.

BACKGROUND: It has been suggested that oxidant stress may play a role in the pathophysiology of heart failure. However, no definitive information is available because most previous approaches used to measure oxidant stress are nonspecific, inaccurate, and unreliable. METHODS AND RESULTS: To evaluate oxidant stress in the heart, we measured pericardial fluid levels of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a specific and quantitative marker of oxidant stress in vivo, in a series of 51 consecutive patients with ischemic and/or valvular heart disease referred for cardiac surgery. Pericardial levels of 8-iso-PGF2alpha were correlated with the functional severity of heart failure (NYHA classification) and with echocardiographic indices of ventricular dilatation measured by independent physicians. Pericardial levels of 8-iso-PGF2alpha were significantly increased in patients with symptomatic heart failure compared with asymptomatic patients and gradually increased with the functional severity of heart failure (P=.0003). In addition, pericardial levels of 8-iso-PGF2alpha were significantly correlated with left ventricular end-diastolic and end-systolic diameters (P=.008 and .026, respectively). CONCLUSIONS: Pericardial levels of 8-iso-PGF2alpha increase with the functional severity of heart failure and are associated with ventricular dilatation. These data suggest an important role for in vivo oxidant stress on ventricular remodeling and the progression to heart failure.

Adult↗
PubMed1998

Energy expenditure during allogeneic and autologous bone marrow transplantation.

Resting energy expenditure (REE) was measured by indirect calorimetry during allogeneic and autologous bone marrow transplantation in order to evaluate the evolution in allogeneic and autologous recipient patients. REE values obtained with indirect calorimetry and compared with values using the Harris-Benedict formula were different. Evolution of REE during aplasia were significantly different in autologous and allogeneic recipients with an increase 11.5 ' 10.8 cent for autologous and a decrease of - 7.3 ' 8.9 cent in allogeneic bone marrow transplantation (BMT) patients. There were no differences in nutritional status and REE before BMT, at discharge and 1 month after discharge between the two groups but all patients had inflicted damage on their nutritional status at discharge from hospital after BMT. However, these patients differed because of the decrease in oral nutritional intake and an increase in the length of aplasia and hospital stay in allogeneic patients. Currently, there is no proof that recommendations for nutritional interventions or results of nutritional investigations in allogeneic BMT can be extrapolated in autologous patients. Harris-Benedict formula does not estimate the energy expenditure of patients submitted to massive chemotherapy and BMT with enough precision because of the great differences in individuals.

Adult↗
PubMed1998

Cardiac troponin I in diagnosis of perioperative myocardial infarction after cardiac surgery.

OBJECTIVE: The diagnosis of perioperative myocardial infarction (PMI) after cardiac surgery remains an important issue. The present study was designed to determine the relevance of the measurement of serum cardiac troponin I (cTnI, a biochemical marker with high cardiospecificity. Therefore, cTnI was compared with creatine kinase-MB (CK-MB) mass and to the other classical signs of myocardial infarction after cardiac surgery. DESIGN: A prospective study. SETTING: A university hospital. PARTICIPANTS: Forty-one patients undergoing coronary artery bypass grafting (CABG) (n = 17) or valvular replacement (n = 24). These patients were separated into three groups according to postoperative complications: group 1, Q-wave PMI (n = 5); group 2, nonspecific changes (non-Q wave) on the electrocardiogram (ECG) and/or need of inotropic support (n = 12); group 3, no postoperative complication (n = 24). INTERVENTIONS: Postoperative follow-up consisted of serial determination of different biochemical markers (CK, CK-MB, cTnI), ECGs, and echocardiography. Blood samples were drawn before (H0) and 3 (H3), 12 (H12), 20 (H20), 24 (H24), and 48 (H48) hours after the onset of cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: In all patients in group 3, CK-MB and cTnI concentrations increased, and peaked at H12 after CPB (13.4 +/- 7.7 and 7.1 +/- 4.1 micrograms/L for CK-MB and cTnI, respectively). In group 1, cTnI concentrations were significantly higher than in group 3 from H12 until H48 (p < 0.002), peaked later (H24; 59.0 +/- 38.8 micrograms/L), and remained in plateau. In group 2, cTnI peak concentrations were significantly different than in groups 1 and 3 (26.2 +/- 14.8 micrograms/L) and occurred at H24 (as in patients with Q-wave PMI). CONCLUSION: A cTnI concentration less than 15 micrograms/L (mean + 2 standard deviations [SDs] of peak cTnI in group 3) within 24 to 48 hours after cardiac surgery is highly suggestive of the absence of perioperative myocardial necrosis. Because of its higher cardiospecificity than CK-MB mass, and its prolonged release after myocardial necrosis, cTnI might be a useful tool in the diagnosis of PMI after cardiac surgery.

Biomarkers↗
PubMed1998

High-dose chemotherapy with hematopoietic stem cell transplantation in patients with mantle cell or diffuse centrocytic non-Hodgkin's lymphomas: a single center experience on 18 patients.

Between 1985 and 1996, 18 patients with diffuse centrocytic lymphoma (DCL), including nine patients with an established histological and phenotypic diagnosis of mantle cell lymphoma (MCL), received 19 courses of high-dose chemotherapy (HDCT) followed by hematopoietic stem cell transplantation. Five patients received HDCT as consolidation treatment after first-line standard chemotherapy, and 14 after a relapse or progression, including one patient in early relapse after the first transplant. Six patients (33%) were in complete response (CR) prior to HDCT and 12 (67%) were in partial response: 10 (83%) of these 12 patients achieved CR at day 60 following HDCT. With a median follow-up of 30 months after HDCT, the 2-year overall and progression-free survivals of the whole series are 91 and 75%, respectively. The 2-year progression-free survivals are 74 and 75%, respectively, in the MCL and DCL subgroups.

Adult↗
PubMed1997

Peripheral blood stem cell and bone marrow transplantation for solid tumors and lymphomas: hematologic recovery and costs. A randomized, controlled trial.

BACKGROUND: Previous studies have suggested that peripheral blood stem cell (PBSC) transplantation has an advantage over autologous bone marrow transplantation. OBJECTIVE: To compare the hematologic recovery and costs associated with PBSC transplantation with those associated with autologous bone marrow transplantation in patients receiving high-dose chemotherapy for solid tumors or lymphomas. DESIGN: Multicenter, randomized, controlled clinical trial. SETTING: French Federation of Cancer Centers, located in cancer facilities or public hospitals with transplantation units. PATIENTS: Children and adults with solid tumors or lymphomas who were candidates for high-dose chemotherapy. INTERVENTIONS: Bone marrow or filgrastim-mobilized PBSCs. MEASUREMENT: The major and point was the duration of thrombocytopenia (platelet count < 50 x 10(9)/L). An economic evaluation of both types of transplantation was done prospectively to measure costs and cost-effectiveness. RESULTS: 129 patients entered the trial; 64 had PBSC transplantation, and 65 had bone marrow transplantation. The median duration of thrombocytopenia was 16 days in the PBSC group and 35 days in the bone marrow group (P < 0.001). All of the other clinical end points studied (time to last platelet transfusion, duration of granulocytopenia, number of transfusion episodes, and duration of hospitalization) favored PBSC transplantation. A cost analysis showed that total cost was decreased by 17% in adults and 29% in children with PBSC transplantation; thus, PBSC transplantation was clearly more cost-effective than bone marrow transplantation for both platelet and granulocyte recovery. CONCLUSION: Transplantation of PBSCs is associated with more rapid hematologic recovery than is bone marrow transplantation after high-dose chemotherapy for solid tumors or lymphomas. Furthermore, global costs are lower and cost-effectiveness ratios are better with PBSC transplantation.

Adolescent↗
PubMed1997

High-dose carmustine for high-grade gliomas in childhood.

Carmustine (BCNU) has proved to be of value against a variety of primary brain tumors. This agent exhibits a steep dose-response curve in in vitro and animal tumor models and has been proposed for use in high-dose chemotherapy as a single agent or in combination. We conducted a phase II study to assess high-dose BCNU in children with high-grade gliomas. A total of 13 children with high-grade gliomas were treated in a phase II study using high-dose BCNU (800 mg/m2) followed by autologous bone marrow transplantation. Eight patients were newly diagnosed, and five were treated at the time of tumor recurrence. Seven patients had diffuse intrinsic brain-stem gliomas. The response was assessed at 1 month after treatment. Only one objective effect was observed. Five patients had stable disease and seven progressed. The immediate toxicity was mild; however, one patient developed fatal respiratory distress at 50 days after treatment with high-dose BCNU. Dose escalation of BCNU does not seem beneficial in children with high-grade gliomas.

Adolescent↗
PubMed1997

Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas.

The addition of conventional chemotherapy to irradiation has improved the outcome of children with malignant gliomas. The application of high-dose chemotherapy has been proposed as a possible way to increase the response rate and thus the survival in children with malignant brain tumours. High-dose etoposide (500 mg/m2/day x 3) and thiotepa (300 mg/m2/day x 3) followed by bone marrow transplantation were given to 22 patients (age range 4-20 years) with newly diagnosed or recurrent high-grade glioma. The response rate in the 14 assessable patients was 29% with one complete and three partial responses. 5 patients had stable disease, and 5 progressive disease. 2 patients died of treatment-related toxicity. Only 3 patients remain alive disease free 54, 60 and 65 months after high-dose therapy. For children with high-grade gliomas, survival using high-dose chemotherapy is no better than that reported with conventional treatments.

Adolescent↗
PubMed1997

Neutrophil expression of CD11b/CD18 and IL-8 secretion during normothermic cardiopulmonary bypass.

OBJECTIVE: To assess blood polymorphonuclear neutrophil (PMN) activation status during normothermic cardiopulmonary bypass (CPB), the expression of the PMN adhesion molecule CD11b/CD18 was measured. Basal state as well as ex vivo capacity of PMN to be stimulated by a bacterial peptide (FMLP) were investigated. Because interleukin-8 (IL-8) is known to induce CD11b/CD18 expression in vitro in PMN, IL-8 plasma levels were concomitantly measured. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Thirteen patients scheduled for cardiac surgery. INTERVENTIONS: Systemic arterial and pulmonary arterial blood samples were withdrawn at the same moment during the first 4 hours after the onset of CPB. MEASUREMENTS AND MAIN RESULTS: Twenty minutes after the onset of CPB, basal expression of PMN CD11b/CD18 was upregulated, whereas IL-8 plasma levels remained unchanged. The increase in PMN CD11b expression was maintained until the fourth hour after the onset of CPB. At this time, elevation of IL-8 plasma levels was maximal. No differences were found between pulmonary and systemic arterial IL-8 plasma levels, even after aortic unclamping. The capacity of PMN to be stimulated ex vivo by FMLP remained normal. CONCLUSIONS: Normothermic CPB induced a fast increase in CD11b expression, which appeared to be similar to that observed during hypothermia. IL-8 was probably not related to the very early CD11b upregulation, but could be involved in pulmonary PMN sequestration during pulmonary reperfusion and contribute to the maintained expression of PMN CD11b. Although partially activated, PMNs maintain a normal capacity to respond to a further FMLP stimulation and thus to bacterial infection.

Adult↗
PubMed1997

Granulocyte colony-stimulating factor given in addition to interferon-alpha to mobilize peripheral blood stem cells for autologous transplantation in chronic myeloid leukaemia.

In order to potentially mobilize and harvest the Ph cells observed in most patients with chronic myeloid leukaemia (CML) during interferon-alpha (IF-alpha) therapy, G-CSF (filgrastim), 5 microg/kg/d, was administered subcutaneously together with IF-alpha to 30 CML patients in haematological remission but with various degrees of cytogenetic remission, after IF-alpha therapy. Peripheral blood stem cells (PBSC) were harvested using standard aphereses from day 5 of G-CSF Patients underwent one to four (median three) aphereses. Median total yields/kg were 7.6 (range 3.8-25) x 10(8) MNC, 3.4 (0-140) x 10(6) CD34+ cells, and 17 (1.1-107) x 10(4) CFU-GM. No patient had a significant increase in the percentage of Ph+ cells in the bone marrow under G-CSF therapy. The percentage of Ph+ cells in apheresis products tended to decrease between the first and the last apheresis (P = 0.05). 14 patients who were not responsive to IF-alpha were transplanted after conditioning with busulphan 16 mg/kg and melphalan 140 mg/m2. Median time to neutrophils > 0.5 x 10(9)/l was 20 d (16-114 d) and to platelets > 50 x 10(9)/l 18 d (12-149 d). Nine patients had a major cytogenetic response post graft, which correlated with the amount of Ph+ cells reinfused with the graft (P = 0.02). We conclude that this procedure is feasible, allowing the harvest of enough PBSC, some of them Ph- in patients who responded to IF-alpha, to allow autologous transplantation.

Adult↗