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Biomedical subjects

C Parmentier

Publications and source records attributed to C Parmentier.

At least 127 records · Page 7Linked to original sources

Hematopoietic recovery following autologous bone marrow transplantation: role of cryopreservation, number of cells infused and nature of high-dose chemotherapy.

Twenty-nine patients were treated with single or combined high-dose melphalan therapy followed by autologous bone marrow transplantation. Hematopoietic recovery from these treatments was studied. No correlation was found between the number of GM-CFC infused and the time required for hematopoietic recovery. It is suggested that this correlation is only demonstrable for low 'doses' of infused bone marrow cell and/or GM-CFCs. The role of bone marrow cell preservation techniques was examined and results were similar for fresh and cryopreserved bone marrow. The erythrocyte, lymphocyte and granulocyte levels of the patients reported here reached a normal or subnormal hematological steady state 3 months after autograft. Our results confirm the value of cryopreservation techniques. Hematopoietic recovery was short and of the same duration whether the patients were given single or combined high-dose melphalan before autologous bone marrow transplantation. These results also demonstrate the value of such transplantation in shortening the myelosuppression caused by high-dose chemotherapy.

Adolescent↗

Chest computed tomography (CT) in patients with micronodular lung metastases of differentiated thyroid carcinoma.

Forty thoracic CT scans have been performed on 27 patients with micronodular lung metastases of differentiated thyroid carcinoma. Lung nodules were visualized in 14 out of 19 patients (78%) with functioning lung metastases, although their chest X rays were normal. However, only a small number of peripheral micronodules can be visualized by CT scan since the central micronodules remain undistinguishable from adjacent vessel structures. A close relationship has been found between the number of micronodules and the thyroglobulin (Tg) serum level. In patients previously treated by 131I for proven lung metastases and who had no uptake for several years, but in whom Tg remained detectable in the serum, CT scans have shown micronodules in 7 of the 13 patients with normal chest X rays. The present data suggest that these nodules are mainly a result of fibrosis. CT scanning appears to be an important complementary tool with regard to 131I whole body scintigraphies in the radiologic diagnosis of lung nodules and in the assessment of radioiodine therapy.

Adolescent↗

Erythropoietic recovery in human after extended field radiotherapy. Ferrokinetic studies of patients treated by radiotherapy followed by autologous bone marrow transplantation and of patients treated by moderate doses (20 Gy) of radiotherapy.

The ability of human irradiated bone marrow to provide suitable environment for migrating stem cells has been studied in four patients. These had received chemotherapy plus doses of 40 Gy to thoracic vertebrae and sternum, followed by autologous bone marrow transplantation. The erythropoietic activity in the non-irradiated areas was increased but it was low in irradiated areas at 3.5 weeks and undetectable at 6 months after autotransplantation. This shows that no nidation of migrating stem cells actively contributed to bone marrow regeneration after 40 Gy and suggests the existence of environmental lesions. No extramedullary erythropoiesis and no bone marrow extension were found in these patients. Four patients who had received doses of 20 Gy to extended bone marrow volume were submitted to ferrokinetic studies from one to 18 years after radiotherapy. In non-irradiated areas the erythropoietic activity was within the normal range. In irradiated areas, it was significantly lower than in the non-irradiated areas and was intermediate between the erythropoietic activity in the sacrum of six healthy control subjects and in the irradiated areas of the four autografted patients. Bone marrow extension was found in these patients. This study suggests that bone marrow recovery after irradiation might not be an all-or-none phenomenon. It would be of interest to better document the dose-effect relationship.

Adult↗

Human granulocyte colony growth: differences between serum-free and serum-dependent cultures.

Human granulocyte colony formation has been observed in serum-free methylcellulose cultures with Iscove medium, delipidated bovine serum albumin, iron-saturated transferrin, alpha-thioglycerol, oleylpalmitoyl lecithin, cholesterol, and linoleic acid using serum-free human placental-conditioned medium (SF-HPCM) as the source of colony stimulating factor (CSF). Dose-response curves for SF-HPCM indicated a lower sensitivity to colony-stimulating activity in serum-free cultures than in serum-dependent cultures. Gel filtration of SF-HPCM revealed that CSF fractions with molecular weights in the range of 30 kD are inefficient in serum-free cultures, while fractions with molecular weights in the range of 40 kD stimulate granulocyte colony formation in both types of cultures. These results demonstrate that serum constituents modulate the effects of one of the stimulating factors for granulocyte colony formation, and that serum-free culture conditions are essential for establishing the growth factor requirements of the granulocyte lineage.

Cells, Cultured↗

[Evaluation of the diagnostic power of 3 methods for assaying free T4. Results in the diagnostic strategy of hyperthyroidism].

The free thyroxin (FT4) tests of Amersham, Clinical Assay and Corning Medical were evaluated in 240 patients who were suspected of hyperthyroidism. The diagnostic performances of the Corning method were of less value while those of the other methods were equivalent to that obtained with the free thyroxin index for an average cost reduced. Furthermore our results show that T3 determination is better than T4 determination in patients who remained doubtful after FT4. However the development of ultra-short methods of measurement of total thyroid hormone blood levels using fluorescence polarization could lead to reconsider the diagnostic strategy of hyperthyroidism.

Evaluation Studies as Topic↗

Phase I trial of Idarubicin (4-demethoxydaunorubicin) in adult acute leukemia.

Idarubicin (IDR) is a new analog of Daunorubicin (DNR) selected for clinical trials because of its outstanding activity in experimental leukemias of mice and in several experimental models when compared to DNR and Doxorubicin. This Phase I trial was designed to determine the maximal tolerated dose in adult patients with acute leukemia refractory to prior treatment, using intravenously (I.V.) daily treatments for 5 consecutive days. Eleven patients were entered in this study. The initial dose of IDR was 4 mg/m2/d X 5 I.V. The highest dose given was 8 mg/m2/d X 5 I.V. Dose limiting toxicity were gastrointestinal side effects at the 8 mg/m2/d X 5 level (mucositis-diarrhea). Antileukemic activity has been detected in acute non-lymphoblastic leukemia not pretreated with anthracyclines. For Phase II adult leukemia studies using this schedule, it is recommended that the IDR dose should be 7 mg/m2/d.

Acute Disease↗

Histomorphometric study of the enhancement of renal compensatory hypertrophy by ACTH in the rat.

In the female adult rat, renal compensatory hypertrophy is greatly enhanced by hyperadrenocorticism elicited by the administration of ACTH given at a dose of 18 Y/100 g BW/d for 7 days after uninephrectomy (UN). This renotrophic effect of ACTH is particularly prominent in rats drinking a NaCl solution (9 g/l). In the present experiments, we performed histomorphometrical measurements of the glomerular tuft (GT) and the proximal tubule (PT) in the hypertrophying kidney (HK) remaining 7 days after UN in 10 rats treated with ACTH and 7 control animals. The histologic preparations were examined under light microscopy with the "Kontron" image analyzer. ACTH increased the weight of the HK (1213.8 +/- 20.3 mg versus 1037.3 +/- 13.3, p less than 0.001) and determined an enlargement of the cross sectional area of the GT (12559 +/- 3351.3 mu2 versus 10486 +/- 407.5, p less than 0.01) and of the epithelial area of the PT (1751 +/- 40.8 mu2 versus 1586 +/- 41.5, p less than 0.025). These morphometrical data are consistent with the increased Protein/DNA ratio - a marker of cellular hypertrophy - found in other rats studied under the same experimental conditions. The increased weight gain of the HK elicited by ACTH is related to the hypertrophy of the epithelial cells of the PT and possibly to an enlargement of the glomeruli.

Adrenocorticotropic Hormone↗

High-dose polychemotherapy with autologous bone marrow transplantation in children with relapsed lymphomas.

Sixteen children with non-Hodgkin's lymphoma (NHL) who had relapsed were treated with high-dose chemotherapy with BCNU, cyclophosphamide, cytarabine, 6-thioguanine (high-dose chemotherapy [HDC]) and autologous bone marrow transplantation (ABMT). Eleven complete responses were obtained and five patients remain in prolonged complete unmaintained remission 77+ to 152+ weeks after treatment. The best results were obtained in patients with CNS involvement and when this regimen was used after complete remission or partial response was obtained by other means. The results appear to be better in B-cell than in T-cell lymphomas, but the numbers are too small for statistical assessment. The use of ABMT rendered the pancytopenic period short and safe, despite the use of drug doses higher than those previously described for this HDC. The frequency of interstitial pneumonitis, possibly related to pulmonary toxicity of chemotherapy, remains a major concern. These results show that this regimen can help to cure some patients but its toxicity prohibits its use in primary therapy.

Adolescent↗

Short and long term effects of radioiodine treatment on the iodine content of the thyroid gland.

Thyroid iodine content (TIC) was measured in nine patients with hyperthyroid Graves' disease for 5-26 months after treatment with 131I (100-125 muCi/g tissue). In all patients, TIC decreased; in eight patients it became undetectable within 5 +/- 3 (SD) months. This fall was parallel to those of serum T3 and T4 levels and was not prevented by the administration of large doses of stable iodine. In four patients, this decrease was irreversible and they became clinically hypothyroid. In the five other patients, it was partly reversible: the secondary increase of TIC was parallel to those of serum T3 and T4 and to a decrease in TSH levels. These data suggest that during the months after 131I treatment, determination of TIC may help to distinguish transient from irreversible hypothyroidism. The late effects of 131I were studied in 38 patients who had been treated for hyperthyroid Graves' disease from 1.5-22 yr previously. The 16 patients who, at the time of examination, were euthyroid with normal serum TSH levels (less than 8 microU/ml) had a TIC [3.2 +/- 3 (SD) mg] significantly lower than that of 10 euthyroid patients previously treated only with antithyroid drug therapy (16.7 +/- 8.2 mg). A significant negative correlation was found between log basal TSH and log TIC (r = 0.61, P less than 0.001) and a positive correlation between log T4 and log TIC (r = 0.56, P less than 0.002). The T3/T4 ratio in patients with undetectable TIC (19.9 +/- 7.9) was higher than that of the other patients (14.6 +/- 3.2) (P = 0.02, Wilcoxon test). This hormonal profile was not modified by iodide supplementation, which increased TIC only transiently. The turnover of thyroid iodine was accelerated, which appeared to be the consequence of a small thyroid functional mass and of hyperstimulation by TSH.

Graves Disease↗

[Value of immunohistochemistry in the study of medullary cancer of the thyroid. Implications of the results for the concept of the APUD system and of apudomas].

Immunohistochemical studies in medullary thyroid carcinoma demonstrate the presence of C cells secreting calcitonin but also of other cells secreting other peptides or proteins. These different cells exist in the tumor as well as in metastases. These results and other reported in the literature suggest a common ultimobranchial and endodermal origin for these cells.

APUD Cells↗

[Clinical signs in medullary cancers of the thyroid].

Medullary thyroid carcinoma is diagnosed with difficulty and at an advanced stage as a consequence of its rarity and its relatively recent knowledge. Therefore, the extent of the disease is already important at the therapeutic stage and the chance of cure is poor. One hundred and thirty four cases treated in the Gustave Roussy Institut (Villejuif) and the Jean Godinot Institut (Reims) between 1942 and 1983 have been studied retrospectively. One hundred and seventeen of them diagnosed after 1960 have been analyzed. We have pointed out the clinical features which should lead to diagnosis and with present means should assure it with the minimum of delay. We have outlined the multiple endocrine neoplasia syndromes IIa and IIb and repeated the necessity of clinical and biological familial screening, 11 per cent of cases are inherited.

Adolescent↗

[Multiple endocrine neoplasia type 2b. Clinical, diagnostic and therapeutic aspects].

Multiple Endocrine Neoplasia type 2b (MEN 2b) is a rare syndrome. The principal features are: medullary thyroid carcinoma (MTC), dysmorphism, a ganglioneuromatosis and pheochromocytomas. Eight cases of MEN 2b have been observed at the Institute Gustave Roussy, between 1968 and 1983. Seven involved children under 15 years of age. Eight had a bilateral MTC; six had dysmorphism; six had mucosal tongue neuromas. Six were troubled with visceral ganglioneuromatosis of whom two had intestinal obstruction and one urinary chronic retention. One patient had pheochromocytoma with hypertension. From this experience and other data it appears that: the dysmorphism is frequently poorly interpreted; the visceral ganglioneuromatosis is an early and severe feature; it is important to examine the patient for pheochromocytoma; the MTC must be detected by calcitonin dosage after stimulation, and requires total thyroidectomy; familial screening must be done. To improve the poor prognosis of MEN 2b, early diagnosis and aggressive treatment are necessary.

Adolescent↗

[Immunoscintigraphy with emission tomography in cancers of the thyroid].

Immunoscintigraphy (IS) consists of in vivo body structure imaging using a specific labelled antibody to an antigen concentrated in the structure under study. Technically, the image contrast is better when IS is performed with a computerized emission tomography system. High concentrations of carcinoembryonic antigen (CEA) have been reported in medullary thyroid carcinoma and thyroglobulin (Tg) is a marker for differentiated thyroid carcinoma. We used injections of 131-I labelled monoclonal antibodies to CEA and Tg to detect thyroid tumours. A feasibility trial using anti-CEA antibodies gave very encouraging results. However, only tumours larger than 10 cm3 could be detected. Contradictory results were obtained using anti-Tg antibodies but this data must be considered as preliminary. Various means of improving the method and the concept of accessibility of the antigen to the antibody in vivo are discussed. This study shows IS to be a promising experimental technique. Further studies are required to define its clinical indications before it can be advocated for routine use.

Animals↗

Immunoscintigraphy in human squamous lung cancer using monoclonal antibodies.

We describe immunoscintigraphy using a radiolabelled anti-tumor monoclonal antibody 181-23 in 6 patients with squamous lung cancer. Double-label method using simultaneous injections of 131I MAB and 125I control immunoglobulin was performed to evaluate the specificity of MAB localization in the tumor. Immunohistological localization of MAB in resected specimen was obtained by immunoperoxidase technique. All our data are negative but correlated.

Aged↗

[Immunohistochemical and ultrastructural studies of thyroid cancer].

The results of immunohistochemical and ultrastructural studies have improved our understanding and provide a better method of classifying thyroid carcinoma. These techniques have also enabled identification of tumours with composite cell populations. These tumours pose clinical, diagnostic and therapeutic problems, and pose fundamental questions such as the relationship between vesicular and C cells. In addition, these techniques are the only available method of determining in situ within the tumour tissue the exact location of different antigens. This information may contribute to the study of the function of the molecules in question and of their accessibility to antibodies in vitro or in vivo.

Fluorescent Antibody Technique↗

Successful infusion of 40 cryopreserved autologous bone-marrows. In vitro studies of the freezing procedure.

Cryopreservation of human bone marrow may be helpful to use supralethal chemoradiotherapy in order to cure malignant diseases. We report here a cryopreservation procedure from large volumes of human bone marrow which can be applied in routinal use. Whole bone marrow in 10% Dimethylsulfoxide (ME2SO) was frozen at an 1 degree C/min. controlled rate and was stored into liquid nitrogen. After thawing and before infusion, both ME2SO and free hemoglobin were removed. The in vitro recovery of nucleated cells and the myeloid stem cell assay (CFC) were performed as quality control. About 60% of the marrow cells and 40% of the total CFC number were recovered at the end of the procedure. Using this technique, 40 patients (25 children with malignant lymphoma and 15 adults with lymphoma and solid tumors) were transplanted with autologous cryopreserved bone marrow after receiving intensive chemotherapy. Three of them received both chemotherapy and a total body irradiation. Engraftment was achieved in all patients. Rise in leucocyte count (greater than 1.10(9)/l) occurred within an average of 17 days. In conclusion, in autologous bone marrow transplantation, this method of cryopreservation is effective to obtain rapid hematological reconstitution in patients treated for malignant diseases by intensive cytoreductive regimens.

Adolescent↗

[Detection of recurrence in patients with differentiated epithelioma of the thyroid].

Two complementary methods are available for detection of tumour recurrence in patients with treated differentiated thyroid carcinoma: plasma thyroglobulin (Tg) measurement and I 131 total body scans (TBS). Tg is measured during T4 treatment: in patients with no thyroid tissue, detectable Tg levels indicated relapse requiring localisation by TBS. False negative results are rare but have been reported and therefore, it is useful to repeat Tg measurement after TSH stimulation in patients with undetectable Tg levels during T4 treatment. Patients with residual thyroid tissues and an elevated Tg level probably have tumour recurrence, but in most cases, Tg is within normal limits and no conclusions can be drawn. TBS in patients with no thyroid tissue is performed 2 weeks after withdrawal of T3. Patients with residual thyroid tissue have TBS performed after 3 injections of bTSH. Doses of 1 to 5 mCi of I 131 are given and TBS is carried out 3 days later? In conclusion, we can say that these two methods are complementary: Tg levels indicate the need for TBS.

Carcinoma↗