Phase I study of liposomal MTP-PE-activated autologous monocytes administered intraperitoneally to patients with peritoneal carcinomatosis.

We have conducted a phase I study with autologous monocytes activated ex vivo and administered intraperitoneally in nine patients with peritoneal carcinomatosis. Blood monocytes were collected by leukapheresis and then purified by counterflow elutriation (up to 10(9) cells, with a purity of greater than 90%). Ex vivo activation was obtained by incubating these cells with 1 micrograms liposomal MTP-PE/10(6) monocytes for 18 hours in hydrophobic culture bags at 37 degrees C in 5% carbon dioxide humidified air. The activated monocytes were then infused in the peritoneal cavity once a week for 5 consecutive weeks through an implanted peritoneal infusion system, Port-A-Cath (Pharmacia Deltec, St Paul, MN), on an intrapatient dose-escalating schedule (10(7) to 10(9) monocytes). No severe adverse reactions occurred. Toxicity was mild, the chief acute reactions being fever (27%), chills (13%), and abdominal pain (25%). None of the side effects led to dose reduction. No consistent change in hemostatic function, liver function, or renal function was observed. Significant increases in granulocyte counts, neopterine, and acute phase reactants (fibrinogen, C-reactive protein) occurred in the peripheral blood. In vitro monocyte activation was demonstrated by the relapse of procoagulant activity and monokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-alpha [TNF alpha]) in the supernatants of cultured monocytes. Evidence for in vivo monocyte activation was provided by the increase of these monokines in the peritoneal fluids. Kinetic studies with indium-111 (111In)-labeled activated autologous monocytes in five patients suggest that these infused monocytes may remain in the peritoneal cavity for up to 7 days. This locoregional immunotherapeutic approach seems to be encouraging in view of adjuvant therapeutic modality in ovarian cancer patients with minimal residual intraabdominal disease following second-look laparotomy.

Spatial or flow velocity phase encoding gradients in NMR imaging.

We describe time modulated field gradient sequences able to selectively phase encode spatial location or flow velocity in NMR Signals. Two flow conditions are presented: constant flow velocity and simple harmonic flow superposed on steady flow. In each case we show that specific modulated gradients are available in order to discriminate between stationary and mobile protons. The methods are presented in the one dimensional case. The advantages of the phase modulation for flow analysis are the following: the method is sensitive to flow direction, unaffected by the T2, and the stationary and flow parameters are quantifiable factors.

[Value of global ejection fractions based on the presence or absence of left ventricular dyskinesia. A comparison between contrast angiography and angioscintigraphy]. / Validité des fractions d'éjection globales selon la présence ou l'absence de dyskinésies ventriculaires gauches. Comparaison entre l'angiographie de contraste et l'angioscintigraphie.

The total ejection fraction of the left ventricle is studied in 37 patients, most of them with coronary disease, according to two methods: contrast angiography in a single plane and angioscintigraphy (first passage and balanced), in order to compare the results according to the presence or the absence of dyskinesias. The two methods are performed in succession according to the usual views. The population is divided in two sub-groups according to the presence (17 patients) or the absence (20 patients) of segmental abnormalities. Segmental abnormalities are divided into 11 antero-apical aneurysms and 6 infero-posterior aneurysms. The correlations of the ejection fractions calculated according to the two methods and the two views, are usually satisfactory in the two sub-groups and especially as the parietal kinetics is homogeneous. In case of segmental abnormalities of the contraction, there are variations in the total ejection fractions depending on the technique and the views that are used, but the differences are not significant.

[Hypoxia in cirrhotic patients. Apropos of a case]. / Hypoxie des cirrhotiques. A propos d'une observation.

The authors report a case of hypoxia in a non-smoking cirrhotic patient. The pathophysiological hypotheses proposed to date to explain this hypoxia without pulmonary artery hypertension, but accompanied by disturbances of carbon monoxide transport, reveal a common element which is difficult to diagnose and quantify: intra-pulmonary shunts. The authors consider gamma-angiocardiography to be a simple diagnostic procedure.

Quantitative bone scintigraphy: usefulness in the survey of patients treated for bone metastasis of prostatic cancer.

The purpose of this study was to develop a quantitative bone scintigraphy (QBS) method in order to evaluate the evolution of bone metastases in patients treated for disseminated prostatic cancer. Data obtained by whole body scintigraphy after injection of 99mTc-methylene diphosphonate enabled us to define three indexes, GR, R1 and R2. They respectively represent the amount of activity retained in the bones, in the metastatic sites and in pathological sites related to the global activity of the skeleton. Repeated QBSs have been performed on 59 patients with prostatic carcinoma treated for bone metastasis with hormonal therapy. Results of QBS are well correlated to clinical findings, particularly pain evolution. In addition, the calculated indexes of QBS made it possible to distinguish three groups of patients according to regression, stabilization or evolution of their lesions under hormonal therapy. QBS seems to be a sensitive and useful test for the evaluation of the therapeutic efficiency on bone metastases from prostatic carcinoma.

Phase I trial of intravenous infusion of ex-vivo-activated autologous blood-derived macrophages in patients with non-small-cell lung cancer: toxicity and immunomodulatory effects.

The purpose of this phase I study was to evaluate the toxicity and biological activity of autologous blood-derived macrophages activated ex-vivo with recombinant human interferon gamma (rhuIFN gamma) [monokine-activated killer (MAK) cells] and administered intravenously to 11 lung cancer patients once a week for 6 consecutive weeks. Peripheral blood monocytes were collected by leukapheresis and then purified by counterflow elutriation. The MAK cells were generated by culturing the purified monocytes in Teflon bags for 7 days and adding rhuIFN gamma to the cultured cells for the last 18 h. These MAK cells expressed differentiation-associated surface antigen MAX1, and were cytotoxic in vitro against tumour cell line U937. The MAK cells were infused at dose levels from 1 x 10(7) to 5 x 10(8) on an intrapatient dose-escalating schedule. No severe adverse side-effects occurred. Toxicity was mild to moderate [primarly fever (75%) and chills (32%)], non-dose-dependent, and non-cumulative. No consistent change in haemostatic function, or liver or renal function was observed. Dose-limiting toxicity was not reached at 5 x 10(8) cells (optimal dose reproduced for each patient). The maximum tolerated dose was not determined. The immunomodulatory activity of i.v. infused MAK cells was demonstrated both in vivo by significant increases in granulocyte count and neopterin level in the patients' peripheral blood post-infusion and in vitro by secretory products (IL-1. TNF alpha, neopterin, and thromboplastin-like substance) in the culture supernatants. The in vivo traffic patterns of autologous MAK cells labelled ex-vivo with 111In oxine were studied in 7 patients. Gamma imaging showed an immediate but transient lung uptake (less than 24 h), and a progressive uptake of radioactivity in the liver and spleen was seen from 6 h to 72 h post-infusion. Our results indicate that the preparation of high numbers of autologous, blood-derived MAK cells is a feasible procedure, and their transfusion is safe for patients. This immunotherapeutic approach seems to be encouraging from the point of view of establishing an adjuvant therapeutic modality in cancer patients with minimal residual disease.