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Biomedical subjects

M Kremer

Publications and source records attributed to M Kremer.

At least 91 records · Page 5Linked to original sources
PubMed1990

[Preliminary results of cytotoxic monoclonal antibody treatment in pancreatic adenocarcinomas and biliary tract carcinomas].

Fifteen patients with biliopancreatic carcinoma were treated by monoclonal antibodies (12 pancreatic adenocarcinomas, 3 bile duct carcinomas). In 7 cases, a tumor resection was associated with immunotherapy: 5 partial pancreatic resections for stage III and IV disease, according to Hermreck's classification, and 2 biliary resections (Whipple resection for distal duct tumor, biliary and liver resection for proximal bile duct tumor). We use the 17-1.A antibody, an IgG-2a murine monoclonal antibody, either isolated (6 cases) or in association with other monoclonal antibodies (4 cases) or gamma IFN (5 cases). All of these patients underwent leukapheresis. Response to 17-1.A therapy was evaluated by laboratory tests (CA 19-9) and by morphological investigations (US, CT, radioimmunolocalization scanning). The median survival of patients with unresectable pancreatic carcinoma (7 cases), was 7.4 months. For pancreatic adenocarcinoma, treated by resection associated with immunotherapy (5 cases), the median survival was 21 months. Monoclonal antibody therapy was effective in a third of evaluated pancreatic adenocarcinomas (4 clear objective responses) but only transiently except in one patient still alive after 57 months. The low rate of therapeutic responses may been attributed to inadequate doses and the development of human anti-murine antibodies.

Adenocarcinoma↗
PubMed1989

Biodistribution of indium-111-labeled OC 125 monoclonal antibody after intraperitoneal injection in nude mice intraperitoneally grafted with ovarian carcinoma.

The purpose of this work was to study the biodistribution of 111In-labeled OC 125 monoclonal antibody (MAb) with known affinity for ovarian carcinomas in a nude mouse model grafted i.p. with a human ovarian cancer (NIH:OVCAR-3). Tumor uptake 24 h after i.p. injection was higher with intact 111In-labeled OC 125 MAb (28 +/- 7.44%ID/g) than with 111In-nonspecific immunoglobulin (6.86 +/- 1.35%ID/g). The kinetics of tumor uptake also differed, showing a plateau followed by a drop at Day 7 with 111In-OC 125 MAb and a decrease beginning at 24 h with 111In-nonspecific immunoglobulin. Tumor-to-normal tissue ratios ranged between 29.91 +/- 11.85 and 0.68 +/- 0.15 with 111In-OC 125 MAb and between 4.50 +/- 1.06 and 0.53 +/- 0.04 with 111In-nonspecific immunoglobulin according to the normal tissues and the time points considered. Tumor uptake 2 h after injection was the same for F(ab')2 fragments as for intact MAb, whereas maximum uptake at 24 h (18.76 +/- 4.62%ID/g) was lower and was followed by a decrease at Day 4. Tumor-to-normal tissue ratios were in the same range, except for the tumor to blood ratio which was higher and the tumor to kidney ratio which was lower at 24 and 96 h. Maximum tumor uptake was higher after i.p. (30.77 +/- 4.76%ID/g) than i.v. (14.59 +/- 2.70%ID/g) injection. Instead of attaining the plateau noted after i.p. injection, tumor uptake after i.v. injection remained low at 2 h (2.11 +/- 1.66%ID/g), reaching its peak only after 96 h. 131I-OC 125 injected i.p., which reached maximum tumor uptake at 2 h (13.53 +/- 4.25%ID/g), showed tumor-to-tissue ratios ranging between 15.98 +/- 2.63 and 0.96 +/- 0.86, i.e., not very different from those with 111In. After i.p. injection of a radiolabeled colloid solution, maximum tumor uptake was reached at 96 h (20.22 +/- 5.35%ID/g), but with very high nonspecific uptake in liver (31.06 +/- 6.22%ID/g) and spleen (55.23 +/- 14.11%ID/g). These results indicate high, selective tumor uptake of 111In-OC 125 after i.p. injection and demonstrate the feasibility of i.p. radioimmunotherapy of ovarian carcinomas.

Animals↗
PubMed1989

Biodistribution of indium-111-labeled OC 125 monoclonal antibody intraperitoneally injected into patients operated on for ovarian carcinomas.

The biodistribution of 111In-labeled monoclonal antibody (MAb) OC 125 was studied after i.p. injection in 28 patients who underwent surgery for ovarian carcinoma. Group I (eight patients) received intact 111In-labeled OC 125 MAb, Group II (three patients) intact 111In-labeled irrelevant NS, Group III (five patients) intact 111In-labeled OC 125 MAb associated with 20 mg of the same unlabeled MAb and Group IV (12 patients) F(ab')2 fragments of 111In-labeled OC 125 MAb. The patients were operated on 1 to 3 days after i.p. injection, and the surgeon removed large tumor fragments and/or small tumor nodules and, in some patients, collected the residual perfusion fluid from which malignant cell clusters were isolated. Uptake by large tumor fragments at 24 h was low: 0.0031 +/- 0.0032% injected dose per gram (%ID/g) for Group I and 0.0024 +/- 0.0022%ID/g for Group IV. It was moderately higher than that of Group II (0.0014 +/- 0.0006%ID/g) and Group III (0.0015 +/- 0.0007%ID/g). Uptake by small tumor nodules (0.1302 +/- 0.0802%ID/g at 72 h for Group I) and malignant cell clusters (median: 0.3322, with a maximum value of 4.1614%ID/g at 24 h for Group IV) was markedly higher. Tumor-to-normal tissue ratios with OC 125 MAb [intact or F(ab')2 fragments] ranged between 0.1 and 8.5 for large tumor fragments and 2 and 8,700 for small tumor nodules and malignant cell clusters. It would thus appear that RIT is feasible if an appropriate radionuclide can be selected for antibody labeling.

Adult↗
PubMed1988

Cell dynamics in the olfactory epithelium of the tiger salamander: a morphometric analysis.

The factors controlling neurogenesis and differentiation of olfactory receptor cells in adults are poorly understood, although it is often stated that these cells undergo continual turnover after a predetermined lifespan. An interesting model in which to study mechanisms which control olfactory receptor neurogenesis and cell turnover is the tiger salamander, since basal cell mitosis varies with epithelial thickness and location in the nasal cavity. This paper presents a quantitative light-microscopic study of the different cell types within the ventral olfactory epithelium of the tiger salamander using a computer-assisted morphometric analysis of 2 micron sections. The results show that the surface density of olfactory vesicles remained constant throughout most of the epithelium and was independent of nasal cavity location, epithelial thickness and the total number of nuclei per unit epithelial surface area. Histological classification of nuclei into different cell types indicated that the increase in total cell number with epithelial thickness was mainly due to an increase in the number of immature receptor cells since the number of supporting cells varied only slightly and the numbers of basal cells and mature receptor cells remained constant except in the thinnest, most caudally located epithelium. It is concluded that the rate of maturation of receptor cells may be limited by an optimal surface density of olfactory vesicles. That is, when this density reaches 4.5 x 10(4) vesicles per mm2 there is a physical or chemical mechanism which prevents the final maturation of newly developing receptor cells, leading to their accumulation. This mechanism may also account for the variations in basal cell mitosis in this species.

Animals↗
PubMed1987

High degree of satellite association and decreased nucleolar organizer activity in cystic fibrosis subjects.

The effect of colchicine at concentrations of 0.25 X 10(-6) M, 1.0 X 10(-6) M, and 2.0 X 10(-6) M on the degree of satellite association (SA) was estimated in phytohemagglutinin-stimulated lymphocytes of individuals in the following groups: cystic fibrosis (CF) children, obligatory CF heterozygotes, control children, and control adults. In all four groups increasing colchicine concentration caused a higher degree of SA. The degree of SA differed between the two control age groups (children vs adults) only at the lowest concentration. CF patients had a significantly higher degree of SA than CF heterozygotes and than control individuals at all colchicine concentrations; CF heterozygotes had a significantly higher degree of SA than control adults at the low and intermediate concentrations. There was a strong interaction between genotype and colchicine concentration: the differences between the CF patients and the control individuals were most distinct at the intermediate concentration and between the carriers and the control individuals at the low colchicine concentration. Colchicine had no effect on the activity of the nucleolar organizer regions (NORs), as measured by the frequency of the silver-stained NORs (AgNORs), while the frequency of AgNORs in CF patients was significantly lower as compared to control individuals. Yet, the increase in the degree of SA caused by the CF mutant allele involved specifically the satellited chromosomes carrying active NORs.

Adolescent↗
PubMed1987

First results of the application of isozyme analysis to study of Culicoides (Diptera: Ceratopogonidae).

Results of a biochemical study on the genus Culicoides are reported. A method of analysis using six discriminant enzymatic systems was used and the results obtained on zymograms are detailed. A genetic study of C. nubeculosus, based on phosphoglucomutase was carried out. The processing of the data obtained, by means of correspondence analysis, provides an interesting comparative study between morphologically related species.

Animals↗
PubMed1987

[Septicemias caused by Candida and other yeasts. Study of cases observed for 5 years at the University Hospital Center in Strasbourg].

Seventy one files of patients with yeasts septicemia have been studied. This study indicates the influence of factors like age (greater than 50 years), health condition, surgery mainly digestive, severe associated bacterial infections, iatrogenic factors (polyantibiotherapy, catheters, intubation), in the occurrence of these septicemia). Clinical symptoms appear to be mainly fever (93%) accompanied with shudders (26%) and toxi-infectious shock (45%). Diagnosis is made by the isolation of yeasts from the blood cultivated on Sabouraud-Chloramphenicol diphasic medium. Among the responsible yeasts, the genus Candida is predominant (82.2%) with C. albicans (59%) followed by the genera Torulopsis (13.7%) and Trichosporon (2.7%). Medical treatment must associate Amphotericin B and 5 Fluorocytosine.

Adolescent↗
PubMed1987

Immunoscintigraphy of recurrences of gynecologic carcinomas.

In a first, retrospective study, 15 patients with known ovarian carcinoma were injected with 131I-OC 125 F(ab')2 monoclonal antibody (MAb). The sensitivity of immunoscintigraphy based on the number of the tumor sites was 67% (12/18). In a second, prospective study, 29 patients with gynecologic carcinoma were injected with 131I-OC 125 F(ab')2 (24) or 131I-19-9 F(ab')2 (5) MAbs according to the histologic type. Based on the number of tested anatomic sites, sensitivity was 72% and specificity 86%. In two patients injected with both 131I-OC-125 F(ab')2 and 125I-NS F(ab')2 (nonspecific immunoglobulin) 1 and 4 days before tumor resection, tumor uptake of the specific antibody was 2.2 and 4.5 times greater than that of NS. Immunoscintigraphic results were complementary with those of ultrasonography and computed tomography. Finally, in one patient injected successively with 131I-OC 125 F(ab')2 and 111In-DTPA-OC 125 F(ab')2, the recurrent tumor was visualized with both radionuclides, with 111In providing better abdominal tumor contrast but causing much greater liver radioactivity than 131I.

Adenocarcinoma↗
PubMed1986

[Clinical aspects, epidemiology and economic impact of foot epidermomycosis in an industrial milieu].

Fungal infections of the feet are very common in some professions. This has been particularly studied in coal mine workers up to 50 p. 100 of whom were found to have dermatophytosis of the feet. The purpose of this study was to determine the clinical, epidemiological and evolutive characteristics of interdigital and plantar intertrigo of the feet among people working in a coking plant, a potash mine and a motorcar factory. We have also evaluated the cost of treatments in relation to their immediate effectiveness and their preventive effects on relapses. Initially, 208 workers entered the study: 84 (40.7 p. 100) had a mycotic infection (M) and 124 (59.3 p. 100) presented with a non-mycotic (NM) inflammation between the toes and on the soles, characterized by maceration of the skin, hyperhidrosis and bromhidrosis. Change in the lesions under treatment were subjected to statistical analysis. In both M and NM groups the workers were allocated by randomization to a double-blind treatment consisting of: group M: either 2 p. 100 miconazole powder or talcum powder with 2 p. 100 salicylic acid and boric acid; group NM: either 2 p. 100 miconazole powder or ordinary talcum powder. Each subject was seen on at least two occasions after 3 and 12 months of daily foot care and topical treatment. Mycological examinations in group M subjects showed that fungal infections of the feet were primarily due to Trichophyton mentagrophytes or to Trichophyton rubrum. A logistic regression analysis (BMDPLR program) of anamnestic and clinical data (table IV) led to a "mathematical model of the mycotic foot", characterized by 6 main parameters of statistically significant occurrence: a history of interdigital-plantar intertrigo, recurrent in 90 p. 100 of subjects in group M (significant association at 0.1 p. 100); a functional symptom, pruritus, present in 71 p. 100 of subjects with mycosis; the stronger, more disturbing the pruritus, the greater the probability of it being of fungal origin (significant association at 0.1 p. 100); 4 physical signs: lack of maceration (0.1 p. 100), lesions limited to the interdigital spaces and respecting the soles (0.1 p. 100), presence of interdigital fissures (0.5 p. 100) and vesiculation (2.5 p. 100). When the respective diagnostic values of these elementary symptoms were considered, it appeared that their various combinations might have predictive values which could be calculated.(ABSTRACT TRUNCATED AT 400 WORDS)

Computer Simulation↗
PubMed1986

Immunohistochemical antigenic expression and in vivo tumor uptake of monoclonal antibodies with specificity for tumors of the gastrointestinal tract.

Two monoclonal antibodies with specificity for carcinoembryonic antigen and Ca 19-9 gastrointestinal tract tumor associated antigens were infused after iodination with 125I and 131I, respectively, in six patients 3 days and in one patient 4 days before radical surgery for colon or rectal carcinoma. Biopsy specimens from tumor, normal colon, fat, muscle, and skin along with a blood sample were excised at surgery and counting was performed for gamma emission. Fragments were then studied by two independent pathologists for immunohistochemical expression of corresponding antigens using the avidin-biotin peroxidase complex. A correlation study was thereafter performed between the amount of antibody bound in vivo, expressed as the percentage of injected dose per gram of tissue and the quantitative expression of tumor associated antigens, taking into account both the percentage of cells expressing the antigen and intensity of staining. For this limited number of patients a good correlation was found between amount of targeted antibodies and amount of expressed antigens. For carcinoembryonic antigen, r values were 0.69 and 0.90 for each pathologist (with an r value of interobserver correlation of 0.74); for Ca 19-9, values of 0.78 and 0.84 were obtained for each observer, with an interobserver r value of 0.97. Based on this limited study, it may be assumed that the possibility of imaging a given tumor is in part correlated to intensity of antigenic expression at the tumor site; other parameters, like tumor vascularization and blood flow for instance, are, however, to be considered for accessibility of antibodies to corresponding antigens.

Antibodies, Monoclonal↗
PubMed1986

Monoclonal antibodies specific immunotherapy of gastrointestinal tumors.

Monoclonal antibody 17-1A showing cytotoxic properties to GI tract adenocarcinoma cells in vitro and mediating tumor growth inhibition in nude mice, was used as immunotherapeutic agent in 95 patients with various metastatic gastrointestinal adenocarcinomas. Several clinical trials were performed in patients with metastatic disease unaccessible to more conventional therapy of proven efficacy. Results of the different trials are reported here. Tolerance to monoclonal antibody infusion was excellent with minor side effects, except when combinations of several monoclonal antibodies were used. Three complete responses, five partial responses inferior to 50% and 24 stable diseases were noticed. A randomized trial is presently performed in high risk cancer patients with B2 or C colorectal carcinomas with 17-1A as adjuvant immunotherapeutic agent after surgery.

Adenocarcinoma↗
PubMed1985

Enzyme-linked immunosorbent assay to monitor colorectal carcinoma patients treated with a monoclonal antibody (17-1A).

An enzyme-linked immunosorbent assay (ELISA) was compared to a radioimmunoassay (RIA) for the detection and quantification of mouse monoclonal antibody MoAb 17-1A and for measurement of the host response (i.e. anti-mouse immunoglobulin in sera from patients receiving immunotherapy with MoAb 17-1A. Comparable sensitivity and reproducibility were noted with RIA and ELISA but ELISA was more rapid to perform than RIA. Thus quantitative ELISA compared favorably with the RIA for MoAb detection.

Animals↗
PubMed1985

Complementary roles of immunoscintigraphy and ultrasonography.

A female patient raised the problem of detection of a primary tumor after discovery of multiple nodular, apparently metastatic, lung densifications. Immunoscintigraphy using an anti-CEA antibody revealed two hot spots above and to the right of the urinary bladder. Ultrasonography showed a right ovarian cyst and normal echo texture for the uterus. Surgery confirmed the diagnosis of a right ovarian cyst with a macroscopically normal uterus. Pathological examination demonstrated adenoacanthomatous involvement of the walls of the ovarian cyst and of the uterus. The results of immunoscintigraphy were thus determinant in visualizing the expression of CEA by the ovarian cyst and by the uterus and thus in suggesting their malignancy.

Adenocarcinoma↗
PubMed1985

Pharmacokinetic study of radiolabeled anti-colorectal carcinoma monoclonal antibodies in tumor-bearing nude mice.

Monoclonal antibodies (MoAbs) 17-1A and 19-9, which specifically bind human colorectal carcinoma (CRC) cells, were tested for their usefulness in localizing colorectal tumors in nude mice. One of the 131I-labeled MoAbs and an irrelevant 125I-labeled immunoglobulin of the same isotype were injected into nude mice simultaneously bearing a human CRC and a human melanoma. The percentage of the injected dose of antibody per gram of tissue, the CRC/tissue ratios of antibody distribution, and the localization indices were calculated at various time intervals (2 h to 9 days). For both MoAbs, labeling to a specific activity of 10 microCi/microgram by the iodogen method gave optimum immunoreactivity. The accumulation of MoAb 17-1A in CRC reached is maximum at 5 days and remained at this level for up to 9 days postinjection. For MoAb 19-9, which detects a circulating antigen shed by the tumor into the serum, the accumulation in the CRC was maximum at 24 h, and decreased thereafter. The CRC/organ ratios and localization indices for both MoAbs increased with time in the CRC tissue, but remained low and unchanged in the melanoma and normal tissues. Using F(ab')2 antibody fragments, faster kinetics with earlier maximum accumulation, higher tumor/organ ratios, and better localization indices were achieved than with intact MoAbs. The data obtained was useful in defining parameters which must be considered before radiolabeled MoAbs are used in cancer patients for diagnostic purposes.

Animals↗
PubMed1985

[Plasma renin activity and prostaglandin E2 in hypotension induced by nicergoline].

The hypotensive actions of nicergoline, a new alpha 1-adrenoreceptor blocking agent, were studied in six dogs during stable anaesthesia under mechanical ventilation. Systemic haemodynamic parameters were measured before the infusion of nicergoline (500 micrograms X kg-1 in 5 min), and regularly after it during 2 h. Plasma renin activity (PRA), right atrial (V PGE2) and arterial (A PGE2) prostaglandin E2 concentrations measured by radio-immunoassay were collected before, and 10 and 20 min after nicergoline infusion. The mean aortic pressure fell to its lowest figure (-30%) at the 5th min, this being maintained for 45 min. Heart rate and cardiac output remained unchanged. Pulmonary wedge pressure (p less than 0.01) and central venous pressure (p less than 0.05) decreased. All parameters reached their control values in 120 min. PRA was unchanged. V PGE2 (p less than 0.01) and pulmonary extraction in PGE2 (V PGE2 - A PGE2/V PGE2) (p less than 0,05) increased whilst A PGE2 was unmodified. The fall in mean aortic pressure was linked (p less than 0.001) to the increase in V PGE2. Nicergoline infusion induced hypotension by reducing vascular tone of resistance and capacitance beds. Hypotension was related to the vasoplegia and to an inhibition of the rapid pressor control mechanisms. The reasons for the lack of renin release were unknown. V PGE2 release was stimulated by the hypotension. The increase in pulmonary extraction in PGE2 was involved in the maintenance of A PGE2 concentration. Nicergoline gave mild hypotension without reflex sympathetic activation. Its alpha-adrenoreceptor blocking properties were similar to those of prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗