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Biomedical subjects

G Santelli

Publications and source records attributed to G Santelli.

At least 55 records · Page 3Linked to original sources
PubMed1986

[Immunopathological study of acute interstitial nephropathy induced by clometacin].

Clometacin is an antalgic drug with a chemical structure very similar to that of indomethacin; it is widely used in France. We report evidence for a cell-mediated immune mechanism in the pathogenesis of clometacin-induced acute interstitial nephritis. In the interstitial infiltrate of a female patient presenting with this condition, T cells constituted 75% of the total lymphocyte population. Cytotoxic/suppressor T cells predominated over helper/inducer T cells with a ratio of two to one. IgA-secreting plasmocytes were also present (about 23% of the inflammatory infiltrate). Peripheral blood lymphocyte studies showed that pre-incubation of the patient's cells with clometacin resulted in an increased sensitivity to interleukin 2 and a positive syngeneic mixed lymphocyte culture. This study seems to be relevant to the pathogenesis of acute interstitial nephritis induced by nonsteroidal anti-inflammatory drugs.

Acute Disease↗
PubMed1986

Urinary neopterin levels in hematologic malignancies.

We studied urinary excretion levels of neopterin in 30 cancer patients affected by non-Hodgkin's lymphomas, Hodgkin's disease and multiple myeloma compared to 30 healthy subjects. Mean value of neopterin excretion in cancer patients (576.01 +/- 620.37) appeared significantly increased (p less than 0.001) compared to normal controls (134.40 +/- 41.65). A neopterin excretion above the upper normal limit was observed in 23/28 (82%) patients with active disease. A trend to an increased urinary level of neopterin with more advanced stage was observed, namely in patients with bone marrow involvement and constitutional symptoms. We suggest that the evaluation of urinary neopterin levels may be of value in the diagnosis and follow-up of hematologic malignancies.

Adolescent↗
PubMed1986

Schedule-dependent antitumor and toxic effects of thymidine and 5-fluorouracil in AKR and L1210 leukemias.

The effect of thymidine (dThd) on 5-fluorouracil (FUra) toxicity to both leukemia stem cells (LCFU) and hematopoietic stem cells (NCFU) was examined. A dose of 10 mg/mouse of dThd given within 1 h before FUra enhanced FUra cytotoxicity to NCFU by a factor of about 4. This effect was also reflected in the reduction of the LD10. The dose-survival curve of FUra in AKR leukemia was modified by the prior administration of dThd 10 mg/mouse: the cytotoxic effect of FUra was enhanced by a factor of between 100 and 1000 throughout the dose range studied. These findings were reflected in the ILS studies. When given by 'high dose' infusion dThd had only a slight antitumor effect on AKR leukemia, and no effect on L1210. When large doses of dThd were infused concomitantly with FUra they potentiated its cytotoxicity against NCFU, AKR LCFU, and L1210 LCFU in a dose-dependent manner and by a maximum factor of about 70.

Animals↗
PubMed1986

Schedule-dependent cytotoxicity of 5-fluorouracil in mice.

The cytotoxic effect of 5-fluorouracil (FUra) given as a 24-hour infusion against both AKR and L1210 leukemias was quantitated by spleen colony assays. The antitumor effect was enhanced in AKR leukemia but was reduced in L1210 leukemia when FUra was given as a 24-hour infusion compared to when the drug was given as an iv bolus injection. No difference in cytotoxicity was noted for these two schedules against normal hematopoietic stem cells in either AKR or (BALB/c X DBA/2)F1 mice. The pharmacokinetics of FUra given as an infusion was similar in the mice bearing these two transplantable leukemias, which ruled out the possibility that the pharmacokinetics of FUra was the cause of the difference observed. Finally, correlation was good between the spleen colony assays and the therapeutic effect defined by life-span assays for both leukemias.

Animals↗
PubMed1986

Regression of bronchial epidermoid metaplasia in heavy smokers with etretinate treatment.

Forty heavy-smoker (over 15 packets per year) volunteers were selected for and have completed a 6-month etretinate treatment on the basis of an index of metaplasia (IM) greater than 15% determined according to the following procedure: bronchoscopy with systematic biopsies in ten sites of the bronchial tree. Each biopsy was cut into ten sections and an IM was calculated: IM = number of sections with epidermoid metaplasia/number of sections examined X 100. Etretinate, a retinoid derivative, was given orally at the daily dose of 25 mg, at the end of which patients underwent a second fibroscopy protocol. A highly significant reduction of IM (P = 10(-5)) was observed after 6 months of treatment for those of the patients who maintained their smoking habits during treatment. Besides, the four patients who stopped smoking while under treatment and are excluded from the statistical analysis all had a complete regression of metaplasia at the second fibroscopy. No morbidity was due to etretinate or fibroscopy. Etretinate significantly reduces potentially precancerous bronchial epidermoid metaplasia in heavy smokers. Its association with smoking arrest may induce a rapid restoration of bronchial epithelium to normal.

Carcinoma, Squamous Cell↗
PubMed1986

Correlation of bronchial epidermoid metaplasia with level of tobacco consumption in heavy smokers.

One hundred forty-four heavy-smoker (125 males, 19 females) volunteers with at least 15 packet-year of smoking experience (number of daily packets of cigarettes X number of years of smoking) underwent bronchoscopy with systematic biopsies in ten sites of the bronchial tree. No morbidity was related to the fibroscopy procedure. Each biopsy was cut into ten sections and an index of metaplasia (IM) was calculated: IM = number of sections with epidermoid metaplasia/number of sections examined X 100. A highly significant statistical correlation was observed (P = 10(-4)) between the IM and the amount of cigarettes smoked (slope of the curve: 0.23). Sex appeared to play an important role in the incidence of metaplasia, since 84% of the examined females had an IM less than 15% versus 48% of the males (P adjusted for individual tobacco consumption in packet-years less than 0.01). Early study of HLA phenotype (locus A) failed to detect a link between HLA and risk of tobacco-induced epidermoid metaplasia.

Epidermal Cells↗
PubMed1985

Fluorescence as a guide to bronchial biopsy.

The presence of fluorescence was assessed in 34 unselected patients undergoing bronchoscopy, 11 of whom suffered from bronchial carcinoma. Bronchoscopic inspection was carried out with white light and then repeated with blue light after the injection of 2 ml of 10% sodium fluoresceinate. Fluorescence was graded visually. Seventy six pairs of biopsy specimens were obtained. Of 38 specimens from non fluorescent areas, histological appearances were normal in 34. Slight inflammation was observed in three biopsy specimens, and in one there was evidence of tumour even though the specimen was obtained some distance from the primary tumour. Of 38 biopsy specimens from fluorescent areas, histological examination showed appearances of moderate inflammation in 10, severe inflammation in 10, tuberculosis in one, and carcinoma in 11. In six instances histological appearances were normal. Five normal subjects who were smokers were also examined by the same technique. Appearances of metaplasia were found more often in areas showing fluorescence than in areas not showing fluorescence. Bronchial fluorescence is considered to be related to alteration in vascularity and is not specific for carcinoma. The most fluorescent areas are generally the most pathological and visible tumour is very fluorescent, but moderate degrees of fluorescence are difficult to interpret. Biopsy of every fluorescent area seems excessive.

Adult↗
PubMed1985

[Hepatocellular carcinoma in a non-cirrhotic liver. Anatomo-clinical study of 22 cases of hepatectomy. Histo-prognostic factors].

The present clinicopathological study concerns 22 cases of hepatocellular carcinoma in non cirrhotic liver; they all underwent hepatectomy performed in the same surgical unit, and this group is clinically homogeneous. This cancer shows higher frequency in males (17/22), and in ages between 40 and 72. No etiologic relevance is shown. An abdominal mass is detected as first clinical symptom. Macroscopically: the tumor most often appears as a chief nodule 2-4 cm in diameter surrounded by smaller ones, always in close proximity. Histologically: the tumors are usually well or rather well differentiated hepatocarcinomas; 4 of them are fibrolamellar. Because of these macroscopical features and because of the absence of metastasis at the time of laparotomy even in case of recurrence, partial hepatectomy seems justified. A rich reticulin framework and its even distribution seem to be the best morphological signs indicating good prognosis. Long lasting survival, exceeding 11 years for one patient, concerns chiefly fibrolamellar tumors.

Adult↗
PubMed1985

Regression of bronchial epidermoid metaplasia in heavy smokers with etretinate treatment.

40 voluntary heavy smokers (over 15 packets-years) were selected for and have completed a six months etretinate treatment on the basis of an index of metaplasia (IM) greater than 15% determined according to the following procedure: bronchoscopy with systematic biopsies in 10 sites of the bronchial tree. Each biopsy was cut into 10 sections and an IM was calculated: (Formula: see text). Etretinate, a retinoid derivative, was given orally at the daily dose of 25 mg, at the end of which they underwent a second fibroscopy protocol. A highly significant reduction of IM (p = 10(-5)) was observed after 6 months of treatment for those of the patients who maintained their smoking habits during treatment. Besides, the 4 patients who stopped smoking while under treatment and are excluded from the statistical analysis, all had a complete regression of metaplasia at the second fibroscopy. No morbidity was due to etretinate or fibroscopy. Etretinate significantly reduces potentially precancerous bronchial epidermoid metaplasia in heavy smokers. Its association with smoking arrest may induce a rapid restoration of bronchial epithelium to normal.

Carcinoma, Bronchogenic↗
PubMed1982

Correlation between precancerous bronchial metaplasia and cigarette consumption, and preliminary results of retinoid treatment.

Vitamin A and its derivatives, so-called retinoids, can prevent squamous metaplasia induced not only by vitamin A deficiency but also by carcinogenic hydrocarbons. An aromatic retinoid, such as ET1, has been shown to prevent chemically induced papillomas in mice and to amplify certain immunologic reactions. Heavy smokers, 106 volunteers, were submitted to fibrobronchoscopy with bronchial biopsies. An index of metaplasia (IM) was calculated on the basis of microscopical examination of a total of 9,633 sections of 1,010 biopsies. Despite the subjectivity of the estimates of cigarette consumption, this was significantly (P less than 0.02) and positively correlated to the IM. Eighty-five percent of the women had a low IM as compared to only 42% of the men (P less than 0.01), although there was no significant difference in the reported cigarette consumption. Fifty-two subjects had an IM greater than 15% and were given 25 mg ET1 orally daily for 6 months. The bronchoscopy was repeated in 30 patients following completion of the 6-month treatment. The IM was significantly (P less than 0.01) reduced after treatment.

Adult↗
PubMed1981

Histopathology of the thymus of patients with acute lymphoblastic leukemia and lymphoblastic lymphoma in complete clinical remission.

The histologic features of thymuses from three patients who underwent thymectomy for acute lymphoblastic leukemia or lymphoblastic lymphoma in complete clinical remission are described. The thymuses from all three patients were fibrotic with a variability in the appearance of the lobules. Some of the lobules consisted predominantly of epithelial cells with small numbers of mature appearing lymphocytes, while other lobules were expanded and composed predominantly of cells having morphological features of immature lymphoid cells consistent with residual or recurrent disease.

Cell Transformation, Neoplastic↗
PubMed1980

In vivo potentiation of 5-fluorouracil cytotoxicity against AKR leukemia by purines, pyrimidines, and their nucleosides and deoxynucleosides.

The effect of various natural pyrimidines and purines and their nucleosides and deoxynucleosides on 5-fluorouracil (FUra) cytotoxicity was examined against the transplantable AKR leukemia in female AKR mice. The spleen colony assay was used for a quantitative evaluation of the antitumor activity of the combination treatments. The base or nucleoside was administered 15 minutes before each mouse received an injection of 0.6 mg FUra. All of the compounds tested, with the exception of adenine, potentiated the cell-killing effect of FUra. On a molar basis (16-30 mumol/mouse), thymine, uracil, thymidine, and uridine enhanced FUra cytotoxicity more than a hundredfold. 2'-Deoxyuridine and the purine nucleosides and deoxynucleosides had similar potentiating activities between tenfold and fortyfold at 30 mumol per mouse. Finally, glucose, also administered 15 minutes before each mouse received an injection of 0.6 mg FUra, enhanced the antitumor activity of the drug by a factor of about five.

AKR murine leukemia virus↗
PubMed1978

In vivo enhancement of 5-fluorouracil cytotoxicity to AKR leukemia cells by thymidine in mice.

The spleen colony assay was used to examine the effect of thymidine (dThd) on 5-fluorouracil (FUra) cytotoxicity in two transplantable leukemias, AKR (in AKR mice) and L1210 [in (BALB/c x DBA/2)F1 mice], in vivo. A large dose of dThd (10 mg/mouse) could not rescue these cell lines from FUra toxicity. Instead, when dThd was given within 1 hour before FUra, it enhanced FUra cytotoxicity by a factor between 100 and 1,000 in AKR leukemia. That dThd increased the cytotoxicity of FUra only by a factor of 3 in L1210 leukemia suggested a different mechanism of interaction of the two drugs in the two cell lines. Examination in hybrid mice capable of supporting the growth of both leukemias showed the enhancement to be tumor related rather than host related. We also demonstrated a dose-dependent effect of dThd injection 15 minutes before FUra in AKR leukemia. Concerning the kinetics of killing of AKR leukemia colony-forming units (LCFU) following the administration of dThd 15 minutes before FUra, LCFU survival continued to decrease for 24--36 hours following drug administration.

Animals↗