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Biomedical subjects

T Philip

Publications and source records attributed to T Philip.

At least 235 records · Page 13Linked to original sources
PubMed1989

Analysis of parameters for maximal in vitro proliferation and activation of lymphokine-activated killer cells (LAK).

In 15 patients (11 adults, 4 children) who received IL-2 and LAK cell therapy, we analyzed the different culture conditions which could either improve LAK cell activation and proliferation or which could simplify the procedure. Each parameter was assayed on a large scale and compared to standard culture conditions. Indomethacin had no effects, either positive or negative, on proliferation and activation of the cells. Culturing with 10% AB serum increased proliferation but did not modify total lytic activity compared to 2% AB serum. When cells were cultured in a medium with 2% autologous plasma obtained before any treatment, their proliferation was similar to that obtained in medium supplemented with 2% AB serum but the LAK activity was significantly higher. Autologous plasma obtained at day 8 of treatment (48 h after the first cycle of IL-2 and the day of the first cytapheresis) gave similar results to 2% AB serum. None of the 12 patients showed negative effects suggesting the presence of suppressive factors in the sera. Culturing with autologous plasma in clinical trials will lead to a 25% decrease in the total cost of culture and suppress the risk of viral contamination. Excess of granulocytes in the culture (greater than 30%), if the total nuclear cell concentration did not exceed 3 . 10(6) per ml, induced a better proliferation of mononuclear cells without modification of the activation. These results could be due to the liberation of factors by polynuclear cells, or to the loss during elimination of the granulocytes by the Ficoll separation of cells with similar density supporting LAK activity.

Adult↗
PubMed1989

[Primary cerebral tumors in children. II: Topography and treatment].

In part I of this article, we reviewed the general aspects of childhood brain tumors. In part II, we present the most common neoplasms and their treatment. The quality of the surgical resection appears to be of first importance in the prognosis. Progress in radiotherapy and chemotherapy have contributed to the improvement of long-term results. However, they are responsible of late deleterious effects. Further progress in therapy must be assessed with in view a critical evaluation of the quality of life.

Brain Neoplasms↗
PubMed1989

[Immunodeficiency and cancer].

The analysis of cancers associated with immunodeficiencies (either congenital, iatrogenic or acquired) enabled us to define the possible role of these deficiencies in the sequence of events leading to cancer and in particular the emergence of hematopoietic proliferations. Immunodeficiency increases the risk of viral infection, and in severe deficiencies, uncontrolled infections (Epstein-Barr virus) are directly responsible for the appearance of polyclonal proliferations; in moderately severe deficiencies, the hyperstimulation of the immune system by repeated infections increases the number of mutagenic events, but the immortalization of a malignant clone is a late event, which may or may not be linked to a viral infection. On the other hand, some intrinsic congenital or acquired abnormalities of lymphoid cells may be responsible both for immunodeficiency and carcinogenesis (chromosomic fragility). Apart from any immunological reaction, the immune system plays a role in the proliferation and differentiation events in various tissues; and any dysregulation of the latter may indicate the emergence of a cancer.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Interleukin-2 with or without LAK cells in metastatic renal cell carcinoma: a report of a European multicentre study.

Between October 1987 and November 1988, 95 European patients with metastatic renal cell carcinoma have been treated with recombinant interleukin-2 (rIL-2) (EuroCetus) at 18 X 10(6) IU/m2/day (equivalent to 3 X 10(6) Cetus Units/m2/day) according to the West schedule in two trials. 1. Forty-two patients received rIL-2 alone. Median time between initial diagnosis and metastases was three months. Eighty-one percent of the patients had at least two involved sites at inclusion and 86% underwent prior nephrectomy. Twenty-seven patients (64%) received two successive courses. Over 80% of the planned dose was administered in 69% and 44% of patients during courses 1 and 2, respectively. Fever, hypotension, weight gain, rise in creatinine level, hepatic disturbances, anaemia and thrombocytopenia were commonly observed but resolved promptly after completion of therapy. No toxic death was recorded. Two (6%) complete responses (CR), four (13%) partial responses (PR), four stable diseases (SD) and 22 progressive diseases (PD) were observed. The response rate is 6/32 (19%); the median progression-free survival time is not reached at 218+ days (92-394). 2. Fifty-three patients received rIL-2 with lymphokine-activated killer (LAK) cells. Median time from primary diagnosis to metastases was three months. Eighty-five percent of patients had at least two involved sites though 73% had previously undergone nephrectomy. Forty patients (75%) received two successive induction courses. Most patients, i.e. respectively, 77% and 60%, were given at least 80% of the planned dose during courses 1 and 2. Median numbers of LAK cells infused were 13.1 and 11.6 X 10(9) nucleated cells per course, respectively. Toxicity was not different from that described above; no toxic death occurred; five CR (10%), nine PR (18%), 11 SD and 26 PD were observed. The response rate is 14/51 (27%) and the median progression-free survival time is not reached at 7.2+ months (3-13.1). In conclusion, rIL-2, with or without LAK cells, is obviously active on metastatic renal cell carcinoma. The difference in response rate between the two trials is not statistically significant but has to be paralleled with the difference in dose received by the patients rather than with the addition of a cellular therapy. Toxicity was always manageable and reversible. The association of rIL-2 with other lymphokines should represent a major issue to improve the response rate and will be considered in further European studies.

Carcinoma, Renal Cell↗
PubMed1989

[Broncho-alveolar lavage by fibroscopy in immunodepressed children].

Thirty broncho-alveolar lavage (BAL) were performed in order to investigate 30 infectious episodes in immunocompromised children. Twenty patients were previously treated by high-dose chemotherapy and autologous bone marrow transplantation and 6 other patients by conventional methods. A specific etiologic diagnosis was obtained in 16 of 30 episodes (56%), 22 microorganisms were identified by BAL. The most frequently involved microorganism was Candida albicans and the other agents were as follows: 3 cytomegalovirus, 2 Pneumococcus, 2 Pneumocystis carinii, 1 Aspergillosis, 1 syncytial respiratory virus, 1 myxovirus, 1 Pseudomonas aeruginosa, 1 Mycoplasma pneumoniae, 1 Haemophilus influenzae and 1 Escherichia coli. In 5 cases, more than 2 agents were involved. This study emphasizes the diagnostic interest of BAL for infectious diseases of the immunocompromised child. BAL appears to be a non invasive, rapid and reproducible method, and a useful therapeutic approach in the treatment of infectious episodes occurring in grafted children where several microorganisms could be involved at the same time.

Bacterial Infections↗
PubMed1988

Liquid chromatographic profiles of major carotenoid esters in commercially processed California Navel and Valencia orange juice concentrates.

A procedure for establishing profiles of major carotenoid esters in commercially processed Valencia and Navel orange juice concentrates by reversed-phase liquid chromatography (LC) using Sudan 1 as internal standard is described. The procedure involved conversion of 5,6-epoxides in heat concentrated citrus juices to more stable 5,8-epoxides by treatment of extracted carotenoids with hydrochloric acid followed by dual wavelength analyses at 400 and 465 nm using LC. The esters of 5,8-furanoids (auroxanthin and mutatoxanthin) were approximately quantitated at 400 nm without interference from other carotenoids. Cryptoxanthin esters and free cryptoxanthin, lutein esters, citraurin esters and carotenes were approximately quantitated at 465 nm without interference from auroxanthin esters. The furanoid esters varied from 60 to 75% of the total carotenoids in the concentrates. The cryptoxanthin esters varied from 5 to 10% of the total carotenoids in Valencia orange juice concentrates and from 10 to 15% of the total carotenoids in Navel orange juice concentrates. Citraurin esters were present only in Navel orange juice concentrates and beta-carotene content was less than 5% of the total carotenoids in both concentrates. The total carotenoids and individual carotenoids increased with the advance in season in Navel orange juice concentrates which had less than half the amount of total carotenoids of Valencia orange juice concentrates.

Beverages↗
PubMed1988

[Hemoperfusion on charcoal and hemodialysis in acute poisoning caused by methotrexate].

Acute methotrexate intoxication occurred in 4 patients despite adequate alkaline hyperhydration and classical folinic acid rescue. Three of these patients had no previous risk factor. Charcoal haemoperfusion with haemodialysis was promptly instituted and the methotrexate blood levels rapidly decreased, avoiding further renal damage and multisystemic involvement. Chemotherapy could subsequently be performed in 3 of the 4 patients without delay and toxicity. Charcoal haemofiltration appears to be an excellent treatment of methotrexate intoxication.

Aged↗
PubMed1988

Separation and quantitative analysis of some carotenoid fatty acid esters of fruits by liquid chromatography.

The adsorption and partition properties of several fatty acid esters of capsanthin, capsorubin, beta-cryptoxanthin, lutein, violaxanthin and beta-citraurin isolated from fruits were studied by normal-phase (silica) and reversed-phase (octadecylsilane) liquid chromatography using Sudan 1 as internal standard. The separation on a normal phase was based on the functional group of the carotenoids and individual esters of the same carotenoid did not resolve. The separation on a reversed phase was more dependent on the number of acyl carbons than the functional group, and individual esters of the same carotenoid differing only two acyl carbons were separated with a resolution of 3. There was a linear relationship between number of acyl carbons and retention times of the same carotenoid on reversed phase. The separation on a normal phase was the reverse of that on a reversed phase, and a combination of normal-phase followed by reversed-phase chromatography was used for the separation of esters with the same or close retention times.

Carotenoids↗
PubMed1988

Continuous vincristine infusion as part of a high dose chemoradiotherapy regimen: drug kinetics and toxicity.

A 5-day continuous infusion of vincristine (VCR; total dose 4 mg/m2) has been given as part of a high-dose chemoradiotherapy regimen with bone marrow transplantation. Evidence of neurotoxicity, such as weakness, paraesthesia and intestinal hypomotility, was evaluated prospectively in nine patients. Five patients had advanced neuroblastoma and four, relapsed sarcomas, and all had responded to initial conventional-dose therapy. VCR was combined with high-dose melphalan (180 mg/m2) and fractionated total-body irradiation. Plasma concentrations of VCR were measured by radioimmunoassay during and up to 24 h after the infusion. Serum and urine electrolytes and liver function tests were measured during VCR treatment and at regular intervals thereafter. VCR concentration at 1 h ranged from 1.8 to 10.9 (median 6.6) ng/ml, and a steady state was achieved by 13-30 h (median 16 h). Levels above 1 ng/ml were maintained throughout the 5-day period with a mean steady-state concentration of 1.7 ng/ml (range 1.3-2.15). After cessation of the infusion, serum concentrations fell to below 0.25 ng/ml within 24 h. Abdominal pain occurred in one patient, but neither constipation nor ileus was seen. In two patients severe muscle pain occurred in the lower limbs towards the end of the infusion. Significant electrolyte problems did not occur and, in particular, there was no evidence of inappropriate ADH secretion. Transient increases in liver enzymes were common but bilirubin was not elevated during the period of monitoring. This regimen allows a two-fold escalation in the dose of VCR to be administered, producing sustained high serum drug levels without major toxicity.

Adolescent↗
PubMed1988

Immunocytochemical detection of neuroblastoma cells infiltrating clinical bone marrow samples.

To evaluate the feasibility and clinical usefulness of immunocytochemical detection of bone marrow metastases in neuroblastoma, we studied bone marrow samples from patients undergoing intensive therapy, followed in the majority of cases by autologous bone marrow rescue. Two monoclonal antibodies were used in an indirect immunoenzymatic assay to test 384 samples collected from multiple bone marrow sites during 79 staging procedures in 48 patients. Of 578 immunocytochemical tests, 59 (10%) yielded non-evaluable results. Analysis by individual bone marrow sites showed an agreement between cytological and immunocytochemical examinations in 276 of 309 (89%) evaluable tests with 5 A7 and in 179 of 210 (85%) with UJ 13 A. Infiltration by neuroblastoma cells was reported in 9% of samples by cytology, in 6% by immunochemistry with 5 A7 and in 16% with 13 A. Analysis of results by staging demonstrated agreement between cytological examination and immunocytochemical detection with both monoclonal antibodies in 60 of 75 (80%) evaluable stagings. Bone marrow metastasis was detected by cytology in 22% of stagings, by immunochemistry with 5 A7 in 23%, with UJ 13 A in 25%. Detailed analysis of discordant results revealed that they were related partly to bone marrow sampling variability associated with focal and minimal metastasis of neuroblastoma cells. These data suggest the clinical usefulness of immunocytochemical detection as a complementary test to cytological examination for accurate evaluation of bone marrow infiltration in patients with disseminated neuroblastoma.

Antibodies, Monoclonal↗
PubMed1988

Cytogenetic evaluation of bone marrow involvement in Burkitt's lymphoma.

Twenty-six bone marrow samples from 21 patients with Burkitt's lymphoma were examined cytogenetically after short-term culture. Clonal chromosomal changes were detected in one of 18 samples from morphologically normal marrows, and in three out of six samples with verified tumor invasion. Three patients had the translocation (8;14)(q24;q32) and one had t(2;8)(p12;q24). Two samples with suspect tumor involvement (less than 5% putative tumor cells) showed no clonal abnormalities. In two samples without morphologic bone marrow infiltration and with only normal metaphases in short-term cultures, clones with t(8;14)(q24;q32) were revealed after a longer time (3-12 weeks) spent in vitro.

Adolescent↗
PubMed1988

Very-high-dose cisplatin and etoposide in children with untreated advanced neuroblastoma.

Between January and December 1985, 17 children with advanced neuroblastoma who were greater than 1 year old (16 stage IV, one stage III) were administered cisplatin (CPDD, 200 mg/m2) and etoposide (VP-16, 500 mg/m2) as a pilot study of toxicity and response rates for the European Neuroblastoma Study Group (ENSG). The study was designed to assess toxicity of two courses of treatment, and evaluate response rates after this short therapy. The creatinine clearance declined in seven of 15 patients. No patient experienced clinically significant hearing loss, but formal audiometric assessment of nine children revealed characteristic high tone loss in seven patients. Peripheral neuropathy was not seen. Asymptomatic hypomagnesemia (less than 0.7 microEq/L) was frequent, despite routine supplementation. Asymptomatic electrolyte imbalances occurred frequently, but were generally transient. Myelosuppression was severe, but brief. Seven patients required platelet transfusions and seven were readmitted between courses due to febrile episodes while neutropenic. There were no treatment-related deaths. According to strictly defined criteria, 12 of 17 patients showed a partial response (PR), and extensive marrow evaluation showed complete clearing of disease in six of 15 patients. This high-dose regimen, if carefully supervised, is associated with acceptable toxicity, comparable to that seen when the dose of CPDD is spread over several months. The rapidity and degree of response was encouraging and merits further evaluation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

High-dose therapy and autologous bone marrow transplantation in partial remission after first-line induction therapy for diffuse non-Hodgkin's lymphoma.

Seventeen patients received high-dose therapy with autologous bone marrow transplantation (ABMT) when in partial response after induction therapy. There were 11 children and six adults between 3 and 57 years old. Twelve patients were determined to have high-grade lymphoma (ten Burkitt's and two lymphoblastic), and five had intermediate-grade diffuse lymphoma. Ten patients had surgically proven active disease in the abdomen, two had active disease in the bone marrow, and five persistent neurological symptoms. The time interval between diagnosis and ABMT was 2-10 months (median 4 months). Two patients died of progressive disease and two others died while in complete remission (CR) because of toxicity. Thirteen of 17 are still alive and disease free with a median observation time of 2 years. Morbidity was high with 6/17 life threatening reversible complications but overall survival is 75% at 24 months in a group of patients clearly defined as having a very bad prognosis in previous studies.

Adolescent↗
PubMed1988

[Pharmacokinetics of high-dose melphalan (200 mg/m2) in a case of total renal insufficiency].

The pharmacokinetics of the alkylating agent melphalan was determined in a dialysed patient, 30 years old, who underwent unilateral orchidectomy for a malignant testicular tumor. Melphalan was included in a polychemotherapy treatment with eight 1-h infusions of 230 mg of etoposide (VP 16), then one 5-min infusion of 370 mg of melphalan (200 mg/m2) followed by autologous bone marrow grafting (ABMG). In this patient, melphalan pharmacokinetics was different from that of patients without important renal dysfunction for the area under the concentration curve (1,324 mg.l-1.min). However, with a melphalan elimination half-life of 80 min, ABMG could be performed, as usually, 24 h after melphalan administration. Plasma alpha-fetoprotein (AFP) concentrations showed that chemotherapy was efficient. Furthermore, we observed a modification of etoposide kinetics due to melphalan.

Adult↗