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Biomedical subjects

L Mariani

Publications and source records attributed to L Mariani.

At least 19 recordsLinked to original sources

Chinese hamster ovary cells deficient or proficient in O6-alkylguanine-DNA alkyltransferase activity are equally sensitive to X-rays.

In mammalian cells, under aerobic conditions, ionizing radiations and radiomimetic chemical agents can induce an enzymatic activity involved in DNA repair, O6-alkylguanine-DNA alkyltransferase (O6-AT). This catalytic protein is active against alkyl-radical-induced DNA damages. This induction was proposed to be linked to the formation of hydroxyl radicals. The possible involvement of O6-AT in the defense mechanism of the cell against aerobic radiation damage was investigated by comparing the X-ray sensitivity of two Chinese hamster ovary (CHO) cell lines, the first deficient (CHO mex-) and the second proficient by transfection of O6-AT (CHO mex+). The colony-forming ability after X-irradiation was appreciably reduced in CHO mex- in comparison to CHO mex+ cells. Nevertheless, pretreatment of proficient cells with O6-methylguanine, a specific inhibitor of O6-AT, reduced the DNA repair activity but did not modify the degree of sensitivity to X-rays of the CHO mex+ cells. Since the glutathione concentrations as well as the DNA damage amounts induced by X-irradiation were comparable in the variously treated cell lines, these results suggest that the observed induction of O6-AT by ionizing radiation in aerobic conditions could be a generalized rather than a specific response to damage by radicals.

Alkylation

The ability of liver extracts from different-aged rats to repair 'mis-instructive' and 'non-instructive' lesions of DNA.

The ability to repair 'mis-instructive', O6-methylguanine, and 'non-instructive', AP sites, DNA lesions in Fischer 344 rat livers at various ages was determined. Different behaviours were observed. While the AP-endodesoxyribonuclease enzymes displayed a high constant level throughout the animals' lifetime, the O6-methylguanine-DNA methyltransferase activity presented a stepwise modulation (DNA normalisation of results): the O6-MT activity significantly increased within the first month of animal life and enhanced again after 6 months reaching a maximum plateau in the 12-18-month-old animals. Thereafter a net significant decrease of O6-MT enzyme was detected in the 24-month-old group. While the repair of the widely formed AP sites appeared uniformly efficient like 'house keeping' functions, the removal of the rare precancerous O6-methylguanine is age-dependent indicating a decreased protection of the youngest and oldest animals against this 'mis-instructive' damage. However, any extrapolation of the age-associated cancer risk needs further assessment.

Aging

Prevention of local relapses and new localisations of oral leukoplakias with the synthetic retinoid fenretinide (4-HPR). Preliminary results.

This paper analyses preliminary results of a randomised chemoprevention trial in patients surgically treated for oral leukoplakia started in 1988 at the Istituto Nazionale Tumori of Milan with the synthetic retinoid N-(4-hydroxyphenyl)-retinamide (4-HPR). To date 115 patients have been randomised, after surgical excision of oral leukoplakia, to receive 200 mg 4-HPR daily for 52 weeks versus no intervention. 80 patients completed the 1-year intervention, 41 in the control group and 39 in the 4-HPR group. During this period 12 local relapses or new lesions occurred in the control group and three in the 4-HPR group. Only 5 patients interrupted the intervention because of toxicity. No impaired dark adaptation was observed. It is concluded that 4-HPR is well tolerated and seems efficacious in preventing relapses and new localisations during the treatment period. This promising trend needs further confirmation.

Adult

[Laparoscopic treatment of varicocele].

Varicocele is frequently a contributing factor in male infertility. We performed laparoscopic treatment of varicocele in 6 patients. This procedure can be carried out through three ports and allows not only ligation and excision of the dilated testicular veins, but those veins branching through the back of the inguinal canal lower down. It is a quick operative procedure and we completed it within 30 minutes. All the patients have gone home on the 2 days and, to date, there have been no complications. During a follow-up period of 3-6 months it was possible to observe the disappearance of varicocele. It is possible to conclude that the laparoscopic procedure is simple and effective as more traditional methods.

Adult

The effectiveness of danazol therapy in postmenopausal women affected by endometrial hyperplasia.

Forty eight patients in postmenopause affected by histologically confirmed endometrial hyperplasia (34 with simplex and 14 with complex forms) were administered Danazol therapy, 400 mg/day for 3 consecutive months. At the end of treatment, regression of the endometrial hyperplasia was histologically ascertained in 46 patients (95.9%) with disappearance of the metrorrhagia. Endometrial atrophy was obtained in 75% of the cases, while secretive (14.7%) or proliferative (6.2%) aspects resulted in the others. Only 2 patients (4.1%) showed persistence of the hyperplastic endometrium. On the basis of this experience, treatment with Danazol appears to be effective and safe with only scarce and transient side effects. This therapy is therefore proposed as a valid alternative to progestogen therapy in cases of postmenopausal endometrial hyperplasia.

Aged

Spontaneous trigemino-pontine pneumocephalus.

A case of a spontaneous trigemino-pontine pneumocephalus in a 25-year-old man without any known risk factors is described. Other cases of spontaneous pneumocephalus in the literature are briefly reviewed.

Adult

[Cytological history of 101 patients with invasive cancer of the uterine cervix].

The cytological history of 101 patients affected by cervical cancer was examined. Three different groups of patients were identified: Group I included 73 women (72.3%) who had never submitted to a cytological cervical sampling, Group II included 17 (16.9%) with an unsatisfactory cytological history and Group III included 11 (10.8%) with a satisfactory cytological history. The disease stage at the time of hospitalization was evaluated in all three groups. In group I, the diagnosis of Stage I was made in 43% of the cases while in the second and third groups, this same stage was diagnosed in 75% and 80% of the cases respectively. Three of the patients from group III presented a normal cytological history, while the other 8 had an abnormal cytological response. Sixty five percent of these 8 had not been submitted to further cytological testing briefly thereafter. From an analysis of these data, the authors attempted to identify the reasons for unsuccess which are still today related to a screening program such at that for cervical cancer. Various international proposals on the organization of a screening program are considered with particular attention given to the minimum and maximum age limits of the women selected for the screening with reference to the authors' personal experience.

Adult

[Psychologic reactions of patients undergoing magnetic resonance imaging. Preliminary study].

MR imaging, like other imaging techniques, can cause emotional and psychological reactions in the patients. Although reversible, these reactions sometimes lead the patient to absolutely refuse the examination or to make it impossible to carry it through. To investigate the patients' emotional distress, a study group of 28 subjects was examined. They were heterogeneous in sex, age, and pathologic condition. The main psychological reactions were analyzed, and anxiety--both of state and of trait. The anxiety parameter was evaluated as a specific index in the psycho-behavioral modifications induced by MR examination. The influence was also considered of the "fantasies" related to examination results on the patients' psyche. Talks and STAI X1 and STAI X2 were employed to this purpose, to identify possible disturbing elements related to both patients' character and examination situations. Our results point to anxiety as the major reaction observed in the subjects undergoing MR examination; it seems to be related to different parameters, which are difficult to identify. Claustrophobia, pathofobia, and the fear of an unknown examination play a major role. Talking to the patients and informing them of the characteristics of the examination proved useful to significantly reduce their emotional distress.

Adolescent

[Manual and mechanic anastomosis. Comparison in oncologic surgery of the colon and rectum].

Personal experience in the treatment of 60 cases of cancer of the large bowel with left hemicolon and rectal localisation is reported. 20 manual double layer anastomoses (group I), 20 single layer (group II) and with mechanical stapler (EEA stapler) (group III) were carried out in consecutive series. The results are reported in terms of early local and general complications: specifically 13 cases of anastomotic dehiscence of which 69.2% were observed in group I, 15.4% in group II and 15.4% in group III. Total postoperative mortality was 5%, average hospitalisation was as follows: 19 days group I, 14 days group II, 17 days group III. The value of single layer anastomoses, which is comparable to results with the stapler whose use is essential in cases of real manual technical difficulty, is stressed.

Adult

Clinically useful measures to assess the effectiveness of treatments: hints for a proper choice with special emphasis on cancer research.

Several absolute and relative measures useful to assess the consequences of treatments in cancer research are presented together with statistical methods suitable for computing the pertinent confidence intervals. The relationship of these measures with the parameters of the regression models commonly used in the analysis of survival data is elaborated upon. Three examples are elaborated, and conditions of interchangeability of the measures are discussed in detail. Finally, suggestions for the choice of the measure most appropriate for a specified data set are given.

Clinical Trials as Topic

DNA repair systems in early and persistent hepatocyte nodules in the rat.

The repair of three DNA lesions, namely O6-methylguanine, 7-methylguanine, and 3-methyladenine, was investigated within early and persistent hepatocyte nodules generated in Fischer 344 rats by a modified Solt-Farber procedure (diethylnitrosamine initiation followed by a 2-acetylaminofluorene/CCl4 cycle). The O6-methylguanine-DNA methyltransferase concentration within both hepatocyte nodule types was always higher than that found in age-matched controls (normal, initiated-only and promoted-only livers). As far as 3-methyladenine and 7-methylguanine-DNA glycosylases are concerned, the early hepatocyte nodules showed far higher activities for both enzymes than were found in the controls, whereas in the persistent ones they underwent a significant decrease. In conclusion hepatocyte nodules are endowed with a high DNA repair activity, which is partly adaptive, partly constitutive; along with others, such a defence mechanism could allow transformed cells to resist many cytotoxic drugs.

Animals

Mutagenicity in V79 cells does not correlate with carcinogenity in small rodents for 12 aromatic amines.

The aim of this investigation was to study the correlation between carcinogenicity in small rodents and mutagenic potency of aromatic amines, as measured by the induction of 6-thioguanine resistance in V79 Chinese hamster cells. It has been previously shown that the carcinogenic potency of these compounds is not correlated to their ability to induce DNA breakage, SCEs, or point mutations in bacteria, but a correlation exists with autoradiographic DNA repair test (in primary hepatocyte cultures). Twelve aromatic amines were tested and the rat liver S9 fraction was routinely incorporated in the mutation assay; mouse liver and hamster liver S9 fractions were also used as metabolizing systems. The comparison of the ranks of mutagenic and oncogenic potencies by means of the Spearman test shows no correlation between carcinogenicity and V79 cell mutagenicity of the tested aromatic amines. There was a generally low mutagenicity seen for aromatic amines in V79 cells. In some cases this could be attributed to an insufficient metabolic activation by rat S9. For example, benzidine, which was inactive when assayed in the presence of rat S9, became mutagenic when in the presence of mouse S9. On the other hand, hamster S9, which has been shown to be the best activating system for 2-acetylaminofluorene in the Ames test, did not activate this compound in V79 cells. Inadequate metabolic activation of the standard system (rat S9) used in this work could explain the low mutagenicity and the lack of correlation observed between mutagenicity and carcinogenicity. A second possibility is that point mutation is not the essential end point for the initiating activity of aromatic amines during the carcinogenic process. A third possibility is that the activity of some aromatic amines is not restricted to the initiation step in carcinogenesis. Chronic treatments with the sublethal doses often result in significant promoting activities, which could mask efficiently the initiating potential of the same chemicals.

Amines

3H-thymidine-labeling index as a prognostic indicator in node-positive breast cancer.

The prognostic relevance of 3H-thymidine-labeling index (3H-TdR-LI) was retrospectively evaluated in 523 women with resectable node-positive breast cancer given adjuvant combination chemotherapy consisting of cyclophosphamide, methotrexate, and fluorouracil (CMF) +/- Adriamycin (doxorubicin; Farmitalia, Carlo Ezba, Italy). The 5-year relapse-free survival (RFS) and overall survival (OS) rates were significantly higher for patients with slowly proliferating tumors (3H-TdR-LI less than or equal to 2.8%) compared with rapidly proliferating tumors (RFS, 66% v 50%, P = .0007; OS, 85% v 73%, P = .0012). In the analysis of RFS, 3H-TdR-LI provided prognostic information independent of axillary node involvement, tumor size, and estrogen receptor (ER) status, with an estimated lower hazard ratio compared with the degree of nodal involvement, but equivalent to that of the other indicators. Conversely, nodal involvement was found to interact with 3H-TdR-LI and receptors on survival. Present findings confirm that tumor cell kinetics represents a prognostic indicator also in an adjuvant situation. 3H-TdR-LI can substantially contribute to a more precise definition of high-risk patients within subsets having the traditionally favorable prognostic characteristics.

Analysis of Variance

Malignant fibrous primary histiocytoma of the recto-vaginal septum.

Considering the different localizations of malignant fibrous histiocytomas (MFH), that of the recto-vaginal septum is extremely rare. The present report describes a case, probably the first in literature, characterized by a storiform-pleomorphic histological type, treated with posterior exenteration and adjuvant chemotherapy. The Authors stress the still controversial histogenetic problem, as well as those related to a correct therapeutic approach.

Combined Modality Therapy

[Desmoid tumor and Gardner syndrome: a little known surgical dilemma. Presentation of 2 cases].

Two patients affected with Gardner's syndrome and desmoid tumour are presented: a 35-year-old man without polyposis coli who developed a clavicular posttraumatic desmoid tumour, and a 52-year-old woman with polyposis coli who died of an intra-abdominal desmoid tumour 3 years after prophylactic colectomy. A close follow-up of patients with Gardner's syndrome for early detection of desmoid tumours after surgery is recommended.

Abdominal Neoplasms

[Anesthesiologic assistance to children undergoing magnetic resonance].

The paper describes the anesthesiological technique used during magnetic resonance tomography in young patients. The Authors developed a neurosedative technique, based on the balanced use of thiopentone sodium, DBP and atropine, which was used in a large study involving 247 patients between November 1986 and April 1989. The results were found to be excellent in patients treated under day hospital conditions, and the Authors conclude that this method is the most efficacious of all solution tested in pediatric patients undergoing magnetic resonance tomography.

Anesthesia