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Biomedical subjects

I Philip

Publications and source records attributed to I Philip.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Management of suspected heart injuries].

Penetrating cardiac injury has to be ruled out in any patients with penetrating thoracic injuries, even in those with no alterations in vital functions. Undelayed echocardiography should be performed to screen for the presence of pericardial effusion. The first case underlines the risk of cardiac tamponade if the diagnosis is missed. Echocardiography was not performed because no echocardiographist was present at the time, and a high suspicion of a neck vascular injury existed. Sudden deterioration due to the onset of acute tamponade was only reversed by an immediate pericardiocentesis followed by surgical haemostasis. The second patient, although stable, had a large echographic pericardial effusion. Emergent sternotomy revealed a large amount of blood in the pericardial space and two cardiac wounds with one on a coronary artery. Penetrating wounds in proximity to the heart, even in a stable patient, require aggressive attempts at ruling out a cardiac injury. Immediate echocardiography should be systematically performed to screen for pericardial fluid.

Adult↗
PubMed1995

Effects of inhibition of nitric oxide synthesis on TNF alpha serum levels in E. coli endotoxemic rats.

We investigated the effects of nitric oxide (NO) synthesis inhibition on mortality rate and TNF alpha serum levels in rats inoculated with E. Coli endotoxin (30 mg/kg i.v.) Pre-treatment of endotoxemic rats with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis by both the constitutive and the inducible isoforms of the NO synthase, did not change the mortality rate but significantly reduced TNF alpha serum levels. By contrast, administration of aminoguanidine, a more specific inhibitor of the inducible NO synthase, did not modify serum TNF alpha. These results suggest that, in E. Coli endotoxemic rats, NO synthetized by the constitutive isoform of the NO synthase positively modulates TNF alpha synthesis.

Amino Acid Oxidoreductases↗
PubMed1995

Intensive regimen of cytokines with interleukin-2 and interferon alfa-2b in selected patients with metastatic renal carcinoma.

We conducted a Phase II trial using an intensive regimen combining interleukin-2 (IL2), interferon-alfa-2b (IFN), and lymphokine-activated killer (LAK) cells. The aim of this study was to evaluate the toxicity and the efficacy of this combination in selected patients with metastatic renal cell carcinoma. Thirty-one assessable patients were treated with at least one cycle of a regimen consisting of 20 x 10(6) IU/day s.c. IFN for 5 days, followed 2 days later by i.v. injections of 24 x 10(6) IU/m2/day IL2 every 8 h together with i.v. bolus of 5 x 10(6) IU/m2/day IFN every 8 h during 5 days. After a 6-day break, during which four leukophereses were performed, this i.v. combination was administered along with the LAK cell reinjections for a maximum of 5 days. Twenty-seven patients underwent the two parts of the first course of treatment; respectively, 42% and 46% of the planned dose of IL2 and IFN were administered. Several severe toxicities were observed including two treatment-related deaths. Significant tumor responses were observed in seven patients, including two complete remissions. Two of these patients remain alive without evidence of disease 36 and 40 months after treatment, respectively. This intensive regimen of IL2 together with IFN and LAK cells cannot be recommended even in selected patients with metastatic renal cell carcinoma. In addition, our results argue against the concept of a dose-response relationship in this setting.

Adult↗
PubMed1994

[Hemodynamic diagnosis of aortocaval fistula complicating abdominal aortic aneurysm].

A 78-year-old man with a history of hypertension was admitted for a fall with back pain. The blood pressure was at 110/50 mmHg and the pulse at 115 b.min-1. A pulsatile abdominal mass was palpated. No signs of respiratory insufficiency or congestive heart failure were found. The diagnosis of abdominal aortic aneurysm was promptly confirmed by echography. Before laparotomy, a pulmonary artery catheter was inserted for haemodynamic monitoring which showed a high cardiac output, low systemic vascular resistances, increased pulmonary artery wedge pressure and a high SvO2 (93%). This was not consistent with a hypovolaemic shock but rather an aortocaval fistula. After incision and aortic clamping, surgical procedure consisted of transaortic closure of the fistula and restoration of arterial continuity with a prosthetic graft. Initial control of venous bleeding was obtained by passing a Foley's catheter distally and by clamping the vena cava. The postoperative course was initially satisfactory. The patient was extubated, but remained with a major renal insufficiency. After a stay of 15 days in the intensive care unit, he died from nosocomial pneumonia. Aortocaval fistulas are either traumatic or spontaneous. Spontaneous fistulas are more common, and in about 90% of the cases result from a rupture of an atherosclerotic aortic aneurysm. Clinical findings include signs of high cardiac output symptoms of venous hypertension and regional arterial insufficiency. Haemodynamic changes can be of value for the recognition of an aortocaval fistula. Most authors emphasize the importance of preoperative diagnosis, allowing the use of appropriate operative techniques and a prompt control of the fistula. This could decrease haemodynamic instability and transfusion requirements.

Aged↗
PubMed1994

Setting priorities for measures of performance for geriatric medical services.

We undertook a two-round Delphi study of the views of consultant geriatricians in three Health Regions on the relative appropriateness of 12 possible performance measures for geriatric services. We compared geriatricians' responses with those of 44 cognitively-intact day hospital patients. Of 138 geriatricians, 89 responded to the first round postal survey, 84 to the second round. The rank order of geriatricians' suggestions did not change from round one to round two, and there was convergence of opinion with a significant decrease in the coefficients of variation of the ranks (p < 0.05, Wilcoxon Test). Geriatricians and patients gave high priority to 'reducing disability' and 'improving quality of life', and low priority to 'reducing mortality'. Geriatricians gave higher priority than patients to 'consumer satisfaction', 'problem resolution' and 'efficient use of resources'. Patients gave higher priority to 'reducing burden on carers', 'measures of service activity' and 'avoiding institutional care'. The study shows that it is possible to obtain a consensus amongst geriatricians about the priorities for measuring the performance of geriatric medical services. Similarities to and differences from patients' views illustrate the need to engage more than one group in the debate about appropriate measures of performance. Findings in both groups give support to recent attempts to develop and use assessment methods for the measurement of disability and quality of life in clinical practice.

Activities of Daily Living↗
PubMed1994

Successful blood stem cell collection and transplant in children weighing less than 25 kg.

Peripheral blood stem cells (PBSCs) were collected for autotransplantation in 20 children (median age 4 years, range 0.5-10 years) weighing < 25 kg (median 14.5 kg, range 6.8-24 kg) with various malignant diseases: leukemias and lymphomas (n = 6), solid tumours (n = 14). Cytaphereses were carried out after standard chemotherapy (n = 10), mobilizing high-dose chemotherapy (n = 9) or radiotherapy alone (n = 1). In 13 children PBSCs were harvested after haematopoietic growth factor (HGF) administration. PBSCs were collected using a continuous flow blood separator (Cobe Spectra). In 13 patients access was through a central catheter with peripheral venous return, in 4 patients access was through a central catheter with return through a femoral catheter; one patient had femoral catheter access with peripheral venous return and two patients had both access and return through peripheral veins. For 19 patients the extracorporeal line was primed with red blood cells. The median blood flow rate was 13.8 ml/min (range 7-22 ml/min). Sixty-six procedures (mean 3.3/patient, range 1-4) were performed with a mean total collection time of 8.5 h. The median number of granulocyte-macrophage colony-forming units (CFU-GM) collected was 37.7 x 10(4)/kg (mean 107 x 10(4)/kg, range 1.05-882 x 10(4)/kg). The number of CFU-GM collected per procedure in children with HGF was 7.8-fold higher than in children without HGF (median 20.4 versus 2.6 x 10(4) CFU-GM/kg body weight, respectively). There were no consistent effects on peripheral blood counts except on platelet counts which decreased following each procedure (median decrease in platelet count was 36%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1994

Circulating cytokines in patients undergoing normothermic cardiopulmonary bypass.

To determine the cytokine release during normothermic cardiopulmonary bypass, we have measured plasmatic levels of tumor necrosis factor-alpha and interleukins-1 beta, 6, and 8 in 10 patients during the first 24 hours after the start of bypass. Arterial blood samples were collected at intervals before, during, and after bypass. Interleukin-1 beta was not detectable in the plasma, and traces of tumor necrosis factor-alpha were detected in only three patients at times independent of the cardiopulmonary bypass procedure. Circulating endotoxin remained undetectable. Plasma interleukin-6 and interleukin-8 rose significantly from 2 until 24 hours after the start of bypass (p < 0.05) and peaked respectively at 4 and 2 hours after the beginning of bypass (interleukin-6, 268.1 +/- 131.43 pg/ml; interleukin-8, 370 +/- 420 pg/ml; mean peak +/- standard deviation). Peak values of interleukin-6 and interleukin-8 were correlated neither with the duration of aortic crossclamping or the bypass procedure nor with the hemodynamic parameters recorded at the same times. This study shows that normothermic cardiopulmonary bypass does not induce systemic release of tumor necrosis factor-alpha and interleukin-1 beta. A local production of these cytokines cannot be excluded, because interleukin-6 and interleukin-8 are produced by stimulated macrophages and monocytes in response to tumor necrosis factor-alpha and interleukin-1 beta. Our results, at normothermia, show a similar pattern of interleukin-6 and interleukin-8 release when compared with release during hypothermic cardiopulmonary bypass. Interleukin-8, an important chemotactic neutrophil factor, might play a role in reperfusion injuries observed in lungs and heart after cardiopulmonary bypass.

Adult↗
PubMed1994

[Effect of carboplatin on the pharmacokinetics of melphalan administered intravenously].

In order to perform melphalan dosage adjustment, the linearity of melphalan kinetics was studied, in the case of previous carboplatin administration. Eleven patients with various solid tumors entered the present study. Carboplatin was administered during 5 days over 1-hour infusions; the day after, the melphalan test-dose was administered and followed 24 hours after by the complement dose. Melphalan kinetics were determined from only three plasma samples by using bayesian estimation. The present study showed that previous carboplatin administrations induced wide variations of melphalan pharmacokinetic parameters between the two administrations. As part of this protocol, the order of drug administration should be taken into account, in order to perform melphalan dosage adjustment.

Adolescent↗
PubMed1994

[Thromboses of heart valve prostheses: predisposing and prognostic factors based on a study of 41 patients].

Forty one patients were admitted with a diagnosis of prosthetic valve thrombosis. One patient was thrombolyzed successfully, and 40 underwent surgical procedures. In 13 cases, prosthetic valve thrombosis occurred in the first month after valve replacement. 18 patients were in functional class IV of the NYHA classification. Among the thrombosed prostheses, 91% were mechanical, and 61% in mitral position. Adequacy of anticoagulation was the most important risk factor, as this treatment was inappropriate in 20 patients. In 10 other patients, it had been changed for medical (bleeding events, pregnancy) or surgical (non cardiac surgery) reasons. The perioperative mortality rate was high (32.4%). It was 12% in patients in functional class II and 46% in those in class IV (p < 0.05). This underlines the value of early diagnosis, in which echocardiography, especially with a transesophageal probe, takes a major place, allowing prompt surgical treatment.

Adult↗
PubMed1994

[Thrombosis of heart valve prostheses: favourable and prognostic factors based on a study of 41 patients].

Forty one patients were admitted with a diagnosis of prosthetic valve thrombosis. One patient was thrombolysed successfully, and 40 underwent surgical procedures. In 13 cases, prosthetic valve thrombosis occurred in the first month after valve replacement. 18 patients were in functional class IV of the NYHA classification. Among the thrombosed prostheses, 91% were mechanical, and 61% in mitral position. Adequacy of anti-coagulation was the most important risk factor, as this treatment was inappropriate in 20 patients. In 10 other patients, it had been changed for medical (bleeding events, pregnancy) or surgical (non cardiac surgery) reasons. The perioperative mortality rate was high (32.4%). It was 12% in patients in functional class II and 46% in those in class IV (p < 0.05). This underlines the value of early diagnosis, in which echocardiography, especially with a transesophageal probe, takes a major place, allowing prompt surgical treatment.

Adult↗
PubMed1993

High-dose chemotherapy with autologous bone marrow rescue in advanced stage IV neuroblastoma.

In order to better evaluate the role of bone marrow purging procedures in the treatment of stage IV neuroblastoma, two similar groups of patients, prospectively treated during the same period at Léon Bérard Center, Lyon, France, and at Giannina Gaslini Institute, Genova, Italy, were reviewed. 18 children were treated in Lyon with a protocol including induction chemotherapy, surgery and a single course of high-dose chemotherapy followed by purged autologous bone marrow rescue. 21 patients were treated in Genoa with a very similar protocol which did not include purging procedures. Progression-free survival at 6 years was 12% (95% confidence interval 0-24%), without any difference between the two series of patients. The only prognostic factor for long-term survival was the persistence (or not) of bone lesions and the presence of metastatic disease (bone or bone marrow) at graft. The small numbers in the two groups and the very poor outcome make it difficult to conclude on the efficacy of purging.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Indication and limits of megatherapy and bone marrow transplantation in high-risk neuroblastoma: a single centre analysis of prognostic factors.

76 patients with high risk neuroblastoma were treated with one (41 patients) or two consecutive courses (35 patients) of megatherapy. Autologous bone marrow transplantation was scheduled after each megatherapy. Univariate analysis confirmed two prognostic factors in this heterogeneous study population: no bone lesions before megatherapy and age at diagnosis of less than 2 years with 5-year progression-free survival rates of 51% (P < 0.0007) and 53% (P < 0.025), respectively. Both factors were shown to be of independent prognostic significance using the Cox proportional hazard model. Identification of prognostic factors should help to define the interest and limits of megatherapy. We consider that elective megatherapy followed by innovative treatments appears justified in patients with persisting bone disease. In contrast, megatherapy has to be re-evaluated for patients showing a more favourable response pattern and/or young age, ideally in a randomised, prospective trial.

Adolescent↗
PubMed1992

In vitro karyotypic and immunophenotypic characterisation of primitive neuroectodermal tumours: similarities to malignant gliomas.

Monoclonal antibody (Mab) mediated immunotherapy of brain tumours requires the identification of tumour-restricted cell surface antigens. We have characterised four primitive neuroectodermal tumours, which included pineoblastoma, medulloblastoma and ependymoblastoma cultures, that demonstrated in vitro evidence of malignant behaviour (anchorage-independent growth and nu/nu xenograft tumour formation). The cytogenetic findings ranged from normal G-banded and Q-banded karyotypes through mixed near-diploid/hyperdiploid. These cultures resembled the cell surface immunophenotypic spectrum of malignant gliomas. They were distinguished from normal glia in vitro by the expression of restricted fetal mesenchymal, neuronal, myoblastic, melanocytic, epidermal, chondrocytic, lymphoid and epithelial antigens. Certain antigens appeared sufficiently represented among central nervous system (CNS) neoplasms to afford potential targets for Mab-mediated immunotherapy.

Adolescent↗
PubMed1992

Greek immigrant children in southern Sweden in comparison with Greek and Swedish children. III. Energy and nutrient intake.

Greek immigrant children (GI) belonging to the second generation of immigrants in Sweden have been compared with Swedish children (S) and Greek children in Greece (G) regarding energy and nutrient intake. Twenty-four-hour recalls were obtained in the homes of the families. The mean energy intake was the same in all three groups and met the Swedish Nutrition Recommendations. The energy distribution for protein, carbohydrates and fat was also similar. The fat intake was far above the recommended level in all groups. The GI and the G group had a significantly higher mean daily intake of monounsaturated fatty acids than the S group (p less than 0.05 and p less than 0.001, respectively). Children aged four to eight years in the GI group had a significantly higher nutrient density of retinol, vitamin D, riboflavin, vitamin B6, calcium, iron, magnesium and sucrose compared to the G group, but compared to the S group they had a lower nutrient density of retinol, vitamin D, ascorbic acid, niacin, vitamin B12 and selen. The GI children consumed more milk than the G children but as much as the S children and they had started to use enriched low-fat milk in Sweden. In conclusion, the food quality in the GI group was better than in the G group and much the same as in the S group, and, with few exceptions, it met the Swedish Nutrition Recommendations.

Child↗
PubMed1992

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Inflammatory mediators released by macrophages (M phi) are believed to be involved in septic vasoplegia. To investigate the effect of M phi on vascular reactivity, excised rabbit carotids were exposed intraluminally either to peritoneal rabbit M phi, activated by 18 h of incubation with 1 microgram/ml lipopolysaccharide, or to the supernatants (SPN) derived from them. The contractile responses to phenylephrine (PE, 10(-6) M) were determined by measuring changes in diameter using an ultrasonic microdimensiometer 1, 2, and 3 h after the first control contraction. In control arteries (n = 12), PE-induced contractions were, respectively, 102.9 +/- 3.3%, 95.2 +/- 4.1%, and 89.7 +/- 3.8% of the first contraction, after 1, 2, and 3 h. Activated M phi significantly reduced PE-stimulated contractions after as little as 1 h of carotid exposure (percentage of controls at 1, 2, or 3 h: 74.1 +/- 5.6, 57.2 +/- 5.2, and 34.2 +/- 5.6, n = 10, P less than 0.001). The activated macrophage-derived SPN took longer to diminish carotid contractility than the M phi themselves, and became significant only after 2 h. The greater effect of M phi might be due to cooperation between M phi and vascular cells, as suggested by the amplified interleukin-1 release observed after M phi infusion. The presence of the endothelium partially protected carotid contractility from depression by activated M phi. Extraluminal addition of NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis prevented this depression in arteries with or without endothelium. No products of the oxidative pathway of L-arginine were detected in rabbit activated M phi. These results suggest that activation of this pathway in smooth muscle cells seems to be involved in vascular hypocontractility.

Animals↗
PubMed1992

High dose chemotherapy with ABMT in soft tissue sarcomas: a report of 22 cases.

Twenty-two patients with locally advanced or metastatic soft tissue sarcomas received high dose chemotherapy with autologous bone marrow graft. Eleven patients receiving melphalan also received fractionated total body irradiation. Six patients (four in CR and two in PR) were intensified after first line therapy. Thirteen patients were grafted after chemosensitive relapse: seven in second CR, one in third CR, one in first PR, three in second PR and one in fourth PR. Three patients with primary refractory disease were intensified. The overall response rate in 66% in nine evaluable patients. The overall median survival and disease-free survival were 19 and 15 months, respectively. The actuarial survival rates at 2 and 5 years were 40% and 32% respectively. There was one treatment-related death due to infection. We conclude that high dose chemotherapy is feasible and provides reasonable response rates in patients with advanced soft tissue sarcomas.

Adolescent↗
PubMed1991

Coronary and left ventricular hemodynamic responses following reversal of flunitrazepam-induced sedation with flumazenil in patients with coronary artery disease.

The effects of reversal of flunitrazepam-induced sedation with flumazenil on coronary hemodynamics, myocardial oxygen consumption (MVO2), and left ventricular (LV) performance were investigated, in a double-blind trial, in 12 patients with stable coronary artery disease undergoing cardiac catheterization. Coronary sinus blood flow was measured by continuous thermodilution. Arterial and coronary sinus blood were analyzed for oxygen and lactate contents. The determinants of LV performance were obtained from the cardiac output measured by thermodilution and from left heart catheterization data. To reverse flunitrazepam-induced sedation, patients were randomly allocated to receive placebo or flumazenil (by increment, up to 1 mg) at the end of procedure. In the placebo group, no significant hemodynamic changes were observed. In the flumazenil group, heart rate, cardiac index, maximum velocity of shortening, and relaxation time constant were not significantly altered. By contrast, mean aortic pressure and LV end-diastolic pressure (baselines: 90 +/- 5 and 7.3 +/- 4.1 mmHg, respectively) increased (9%, P less than 0.05 and 67%, P less than 0.05, respectively) after flumazenil administration, but these changes represented mainly a return toward presedation values. MVO2 and coronary resistance were not significantly altered, whereas CSBF increased slightly (baseline: 119 +/- 20 ml/min; increase 10%, P less than 0.05). No electrocardiographic evidence of myocardial ischemia was observed during the study. These data show that reversal of benzodiazepine effects with flumazenil is not associated with a major alteration of LV systolic function, relaxation, or coronary hemodynamics in patients with coronary artery disease. Nevertheless, it should be cautiously used when LV end-diastolic pressure is increased at the time of its administration.

Adult↗