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Biomedical subjects

I Philip

Publications and source records attributed to I Philip.

At least 73 records · Page 4Linked to original sources
PubMed1991

Interleukin-2 and lymphokine-activated killer cells in 15 children with advanced metastatic neuroblastoma.

A phase II trial using interleukin-2 (IL2) and lymphokine-activated killer (LAK) cells was carried out in an attempt to treat children with end-stage neuroblastoma. Fifteen patients (median age, 7 years) were enrolled in the study. Twelve were in relapse after massive chemotherapy and autologous bone marrow transplantation (ABMT), and three had a primary refractory disease after conventional chemotherapy. IL2 was administered as an 18 x 10(6) IU/m2/d continuous infusion. One course consisted of a double 5-day treatment period separated by a 6-day break. Cytapheresis to harvest LAK progenitor cells was performed during the rest period. After a 4-day in vitro culture, LAK cells were reinjected during the second cycle of therapy. A phenotypic and functional analysis of immunologic parameters was conducted along with the therapeutic protocol. Toxicity was significant with two toxic deaths (cardiotoxicity and respiratory distress). The reinfusion of large amounts of LAK cells was clearly involved in one case, but this particularly severe toxicity has to be related to the patient's status (ie, heavy pretreatment). No significant clinical response was seen. The immunologic monitoring showed phenotypic and functional modifications in these patients before initiation of treatment and an unexpected absence of evolution of these parameters during IL2 therapy. Although the origin of these immune dysfunctions is not clear, they could be involved in the failure of IL2 therapy. Future studies of IL2 therapy in neuroblastoma should be undertaken earlier in the course of the disease.

Antibodies, Monoclonal↗
PubMed1991

Intravenous interleukin-2 just after high dose BCNU and autologous bone marrow transplantation. Report of a multicentric French pilot study.

This multicentric pilot study was conducted in order to evaluate the feasibility of early interleukin-2 (IL2) after high dose chemotherapy requiring autologous bone marrow transplantation (ABMT). BCNU at 800 mg/m2 was followed, 3 days later, by the reinjection of the bone marrow cells. At day 4, IL2 at 18 x 10(6) i.u./m2/day was given as a continuous infusion during a minimum of 6 days (first phase of study) or for 6 more days after 1 day break (second phase of the study). Twenty patients were included. Toxicity was not negligible, with one toxic death, but IL2 therapy does not damage the haematological recovery of most patients. However, a 6-day IL2 treatment period only appears tolerable. In 18 evaluable patients, three responses were observed: one complete response (CR) of short duration in a non-Hodgkin's lymphoma, one CR (24 months +) and one partial response (PR) (6 months) in two patients with metastatic gastric adenocarcinoma. This study confirms that IL2, restricted to a 6-day treatment period, is feasible immediately after high-dose chemotherapy requiring ABMT without haematological problem in most patients. The response rate was unexpected for a pilot study and this combined therapy obviously requires further study.

Adult↗
PubMed1990

[Hemodilution and peroperative autotransfusion during harvest for bone marrow graft].

In order to avoid the infectious and immunological complications of homologous blood given to autologous bone marrow graft recipients, intraoperative haemodilution together with delayed salvage of the red blood cells contaminating the marrow graft were used prospectively over a period of 6 months. This was carried out in 74 patients, i.e. 2 allogenic and 72 autologous donors (mean age 27.2 +/- 19.7 years). A mean of 13.66 +/- 7.10 ml.kg-1 bone marrow were harvested. Fluid replacement was carried out, volume for volume, with a modified fluid gelatin (Plasmion) (n = 73; 14.6 +/- 6.6 ml.kg-1), glucose 5% (n = 54; 9.64 +/- 4.88 ml.kg-1) and Ringer solution (n = 33; 8.1 +/- 3.3 ml.kg-1). No haemodynamic problems occurred. Autologous blood transfusion was possible in 54 patients; mean volume of bone marrow harvested was 631 +/- 298 ml, and a mean of 293 +/- 154 ml of blood was retransfused to the patients (mean haematocrit of the blood units: 0.536 +/- 0.048). Nine of these patients were also given homologous blood. In the other 20, the volume of bone harvested marrow was significantly lower than in the autologous transfusion group (430 +/- 202 ml; p less than 0.05), and red blood cell salvage was not possible; only 3 patients received homologous blood. Finally only 16.2% of the patients in this series were given homologous blood. It is concluded that intentional isovolaemic haemodilution together with autotransfusion of salvaged blood can reduce the need for homologous blood during bone marrow harvesting.

Adolescent↗
PubMed1990

Greek immigrant children in southern Sweden in comparison with Greek and Swedish children. II. Meal pattern and food habits.

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 meal pattern and food habits. Interviews were performed in the homes. Meal pattern and frequency of consumption of various food items were studied by 24-hour recalls, and the food frequency interview method. The meal pattern and the distribution of meals and snacks during the day did not show large differences between the groups. In the GI and G groups it was common to start the day with milk and sugar. The same habit was reported before going to bed. It was common in the GI and G groups to have a prepared meal (dinner) relatively late in the evening. Of the S children only 55% had dinner. GI children had a less frequent intake of vegetables compared to S and G children. GI and G children were heavy consumers of sweets and snacks. In conclusion, the Greek immigrant group had food habits similar to those of Greek rural children with few distinctive exceptions. Greek immigrant families had no difficulties in preparing Greek food.

Child↗
PubMed1990

Autologous bone marrow transplantation in pediatric solid tumors.

During the last 5 years massive chemotherapy and autologous bone marrow transplantation have been increasingly explored in the treatment of pediatric solid tumors, mainly for neuroblastoma, Ewing's sarcoma, rhabdomyosarcoma, Wilms' tumor, germ cell tumors, osteosarcoma, and retinoblastoma. Although the disease course could be changed successfully in most instances, the long-term survival has not yet been improved much over the best available conventional treatments. Despite this, in responding relapsed patients this approach seems promising and may represent the only chance of cure. New and better induction regimens are needed.

Adolescent↗
PubMed1990

Functional and immunophenotypic modifications induced by interleukin-2 did not predict response to therapy in patients with renal cell carcinoma.

Twenty-five patients with renal cell carcinoma were treated with continuous infusion of IL-2 (3 x 10(6) units/m2/day) with or without lymphokine-activated killer (LAK) cells; 5 responded to therapy. Functional and immunophenotypic modifications of the peripheral blood lymphocytes (PBLs) did not predict response to therapy. Systemic administration of interleukin-2 (IL-2) during 5 days caused a preferential proliferation of natural killer (NK) cells, although CD4+ T cells remained the predominant circulating population, in particular in three of the five responding patients. The IL-2 low-affinity receptor was induced only on CD4+ T cells. B cells did not proliferate and immunoglobulin levels were not modified by IL-2. In the peripheral blood, the NK function increased but the LAK function in vivo remained low. The T-cell proliferative response in mixed lymphocyte cultures (MLCs) decreased after therapy. Four days of ex vivo culture of PBLs with IL-2 did not modify T and NK distributions, but increased the coexpression of CD8 on NK cells and NKH1 density; it decreased the coexpression of CD16 and induced LAK cell function. Three weeks after the end of the first course of therapy and before the second course was started, all immunological parameters returned to baseline levels, except the T-cell proliferative response in MLCs. The second course of IL-2 therapy induced the same modifications as the first one, with the exception of a higher CD4+ T-cell proliferation.

Adult↗
PubMed1990

[Vascular smooth muscle fibers and the autonomic nervous system].

Vascular Smooth Muscle cell (V.S.M.C) plays a major role in the regulation of vasomotion. Sympathetic system play a key role in vascular smooth muscle function. Epinephrine (humoral pathway) and norepinephrine (nervous pathway) can both stimulate V.S.C.M. via delta and beta adrenergic receptors. The function of parasympathetic system is more controversial. Acetylcholine induces the release of a relaxing factor by the endothelial cell (E.D.R.F.) but it has a direct contracting effect on V.S.C.M. Neural vasodilation is also concerned by noradrenergic mechanisms.

Autonomic Nervous System↗
PubMed1990

Lymphokine-activated killer cell expansion for clinical trials of adoptive immunotherapy with interleukin-2: optimization of the culture technique.

On leukopheresis products obtained from patients included in a protocol interleukin-2/lymphokine-activated killer (IL-2/LAK) cell therapy, we analyzed, in parallel with the standard culture and on large volumes of these products, different parameters which could either improve LAK cell enhancement or simplify the procedure. We demonstrated first that purification of the mononuclear cells from the leukopheresis product before its culture is not required. An excess of red blood cells and granulocytes (up to 50%) in nonpurified samples improved both the mononuclear cell recovery in short-term culture (4 days) and the activation of LAK cells when the total nuclear cell concentration did not exceed 3 X 10(6)/ml. Different factors can contribute to this enhancing effect: the presence of red blood cells, the liberation of cytokines by granulocytes, or the loss of a population of activated lymphocytes, with liberation of cytokines by granulocytes, or the loss of a population of activated lymphocytes, with larger size and density than resting lymphocytes, during the separation. Supplementation of the medium with 2% heat-inactivated autologous plasma obtained before any treatment rather than with 2% pooled human AB serum does not modify the mononuclear cell recovery in 4-day culture, but it does enhance LAK activity. The inhibitory effect of heat-inactivated autologous plasma on proliferation and activation of LAK cells was never observed, suggesting the absence of suppressive factors in the plasma of the 23 analyzed patients. Similarly, autologous plasma did not modify natural killer and LAK cell functions when added during the cytotoxic assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Adoptive immunotherapy with interleukin 2 in oncology].

Forty-seven patients with renal carcinoma were included in first line or rescue protocols of immunotherapy including IL2 alone or in association with LAK cells, INF alpha or TNF. The toxicity was mild and the mortality was 2% (1 patient). The response rate was 26%. Nineteen children with neuroblastoma received IL2 either alone or in combination with LAK cells. The morbidity and mortality were higher in patients with end stage disease who had previously received high dose and prolonged chemotherapy. In contrast, the toxicity was mild and transient in patients treated in the months following autologous bone marrow transplantation. The only complete response observed was in 1 child treated with IL2, 4 months after high dose chemotherapy and ABMT. Immunological analysis showed that the immunomodulatory effect of IL2 is very different depending on whether IL2 is used alone or in combination with other cytokines; moreover, the biological effect of IL2 is dependent on the immunological status of the patients prior to IL2 therapy.

Adenocarcinoma↗
PubMed1989

Clinical value of N-myc oncogene amplification in 52 patients with neuroblastoma included in recent therapeutic protocols.

Southern blot analysis of neuroblastoma (NB) cell DNA from 52 patients (58 samples) allowed the detection of an N-myc amplification on three of the 13 BM samples and three of 13 tumor samples at diagnosis, on two of 17 tumor samples taken after induction therapy, on three of seven BM samples and two of the five local tumor samples taken after relapse. N-myc was amplified in two of the 15 patients with stage I to III NB and in 10 of the 36 patients with stage IV neuroblastoma over 1 year of age. Conclusions from the analysis are as follows: first tumor samples obtained on previously treated patients are histologically modified and detection of N-myc amplification is not accurate; consequently N-myc amplification must be defined at diagnosis. Surgical biopsies of the primary tumors can, however, be delayed and malignant cells obtained by ultrasound-guided punctures or analyzed on bone marrow samples if they represent more than 50% of the total population. Second, any attempt to define the prognostic value must be performed on a group of patients treated with a new aggressive protocol of chemotherapy; it will require a multiparametric analysis including, in particular, results of an extensive clinical staging at diagnosis and histological criteria.

Child↗
PubMed1989

Interleukin-2 with and without LAK cells in metastatic renal cell carcinoma: the Lyon first-year experience in 20 patients.

Thirty-one patients with metastatic renal cell carcinoma were seen at the Centre Léon Bérard from October 1987 to October 1988. According to our protocol, 11 were excluded leaving 20 in the study. The median age was 55 years (range 36 to 79 years). The median number of metastases was 9 (range 2 to 29) and the median number of metastatic sites was 3 (range 1 to 4). Seventeen patients received a continuous infusion of recombinant interleukin-2 (rIL-2) of 3 x 10(6) U/m2/day, on days 1 to 5, with lymphapheresis on days 7 to 10 and IL-2 + LAK on days 11 to 15. Three patients received IL-2 alone. The clinical toxicity of IL-2 was as expected (100% fever, 88% erythema, 88% vomiting, 87% weight gain, 76% oliguria, 76% diarrhoea, 70% pruritus, 70% weakness, 41% severe hypotension, 41% acute renal failure, 33% disorientation, 23% respiratory distress, 12% ventilation and 5% coma) with no toxic deaths. Other toxicity was mild (median platelet nadir was 93,000 and median nadir of Hb 8.1 g/dl) except for the creatinine level which was found to be between 200 and 400 mumol/l in 45% of the courses and over 400 mumol/l in 24% of the courses. Eight capillary leak syndromes were observed. Among the three patients receiving IL-2 alone, one PD, one SD and one early toxicity were recorded. Among 15 evaluable patients receiving IL-2 + LAK, three had PR (20%) and two mixed response (PR and progression before 2 months); two had stable disease and eight had progression. No clinical or biological factor was able to predict response. However, the five objective responses were observed among the eight patients with a capillary leak syndrome. Lymphocyte peaks or platelet nadir were not related to response in this group of patients. The median number of harvested mononuclear cells was 9.8 x 10(10) and the median number of mononucleated cells reinjected was 5.9 x 10(10).

Carcinoma, Renal Cell↗
PubMed1989

Immunological detection of neuroblastoma cells in bone marrow harvested for autologous transplantation.

In about 50% of patients with stage IV neuroblastoma, micrometastases are present in the bone marrow when it is harvested for an autograft to follow induction therapy, and the risk of graft contamination by neuroblastoma cells has been the rationale for the use of a purging procedure. However, bone marrow metastases are detected with trephine biopsies which only explore the sites biopsied and do not reflect potential contamination of the pooled marrow harvested for autograft. A two-colour fluorochrome labelling method is described which permits as few as 1 neuroblastoma cell in 100,000 normal bone marrow cells from the autograft to be detected. Three monoclonal antibodies (UJ13A, H11 and 11.14) which react with neuroblastoma cells are used as single reagent in combination with a fourth anti-panleucocyte antibody. This method requires only 2 h for the analysis of three million marrow cells from the autograft, and is more effective than alkaline phosphatase staining with the same monoclonal antibodies. Results were compared with conventional techniques (four biopsies and four aspirates) carried out at the same time in 34 consecutive patients. Of 18 cases with negative aspirates and biopsies, neuroblastoma cells were detected in two autografts by the immunological method. Of 16 cases with positive aspirates and/or biopsies, 10 autografts were positive by the immunological method and six were negative. Thus, marrow micrometastases were detected in 16 of the 34 patients, but the autograft contained malignant cells in only 12 of these patients and the immunological analysis demonstrated that the use of a purging procedure allowed the elimination of neuroblastoma cells from the autograft before its reinjection to the patients.

Antibodies, Monoclonal↗
PubMed1989

Immunomagnetic depletion of malignant cells from autologous bone marrow graft: from experimental models to clinical trials.

Using experimental modes with normal allogeneic bone marrow (BM) contaminated with Burkitt or neuroblastoma cell lines, and a liquid culture assay, we demonstrated that, when used in optimal conditions, the immunomagnetic depletion technique permitted a reproducible elimination of 3-4 log malignant cells. Results were very similar to those obtained with the complement lysis procedure in Burkitt lymphoma. This immunomagnetic procedure was used in 123 cases of autologous bone marrow transplantation (ABMT) in children with neuroblastoma. The analysis of the cases demonstrated, first, that the procedure induced a significant loss of mononuclear cells but was not toxic for BM precursors. Delays to engraftment observed in a few patients were probably due to the combination of pejorative factors, especially the damage caused to the micro-environment by previous heavy and prolonged chemotherapy or the double ABMT programme. Second, patients presented with profound T-cell defect with undetectable IL2 secretion up to 1 year post-graft but they all had normal NK functions from the first month post-graft, these functions exceeding normal values on the second and third months post-graft. Finally, in 20 cases, dual-immunofluorescence staining permitted the demonstration that the autograft contained malignant cells before purging that were eliminated by the immunomagnetic depletion.

Bone Marrow↗