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Biomedical subjects

L Mariani

Publications and source records attributed to L Mariani.

At least 145 records · Page 8Linked to original sources

[Toxicology of reproduction and development. Pregnancy and periods of risks from drugs].

The authors discuss the possibilities of drug interference with the reproductive system and especially during various stages of pregnancy: from the sequence of neurochemical events that condition the release of pituitary gonadotrophines at the level of the central nervous system to late events that may occur during development. After listing the periods of risk, drug-induced changes in the conceptus are illustrated on the basis of data registered in the literature. In this context, it is stressed that the dysmorphogenic effect is limited to the period of differentiation and organogenesis whereas it is becoming more and more obvious that drugs may also have variable effects on other stages of pregnancy where frequently they have specific pharmacodynamic actions on the fetus. The knowledge of these effects may be useful in order to avoid untoward actions on pregnancy or on embryo, fetus, neonate or postnatal development, but may also create a basis for in utero drug treatments of fetal pathologies.

Central Nervous System↗

[Acute pancreatitis: clinical-tomographic correlations].

The authors are interested in verifying the correlation between clinical findings and CT scan imaging in acute pancreatitis. Forty-one patients with acute episodes of pancreatitis are studied according to classic clinical Ranson prognostic factors and radiological Hill classification. All patients are investigated with G.E. 9800 Quick TC scanner. Our data show a significant correlation especially for patients of extreme classes: 78.3% of patients in first Ranson class are included in 0-I-II Hill grades, 74% of the patients in the cumulative third and fourth Ranson classes are correlated with IV and V Hill grades. Finally the authors underline the usefulness of clinical and tomographic evaluation for prognostic and therapeutical trends in patients with acute pancreatitis.

Acute Disease↗

[Toxicology of reproduction and development. Changes in the male reproductive function caused by drugs and pollutants: potential effects on offspring].

Published clinical observations underline the difficulty of defining with epidemiological studies the effects that chemicals such as drugs, illicit substances environmental and workplace pollutants might have on the offspring through the male parent. The Authors highlight how defining this issue might help both guide preclinical research and evaluate correctly clinical observations which are often difficult to interpret based only on observations in the female parent. Clinical research already available shows that some chemicals are able to modify fertility by acting either at the neuroendocrine level or on the testis. However, it is more difficult to identify and quantify the potential damage to the offsprings during the different phases of pregnancy and postnatal life. Finally, the Authors discuss the parameters that should be considered to obtain an algorithm for evaluating the reproductive risk in males, along the lines of the risk for the embryo and fetus due to the use of drugs during pregnancy. Moreover, it is suggested that among the unwanted effects of drugs and pollutants, those related to the different components and phases of the male reproductive function be reported also in relation to the patient's age.

Environmental Pollutants↗

Effect of menstrual phase on surgical treatment of breast cancer.

1175 premenopausal women whose date of last menstrual period was known were followed up for up to 20 years (average 8 years) after surgery for breast cancer. 525 patients were in the follicular phase and 650 in the luteal phase. We observed 192 unfavourable events among patients operated on during the follicular phase (36.6%) and 192 among patients operated on during the luteal phase (29.6%). The effect of phase was restricted to patients with positive axillary nodes. The 5-year relapse-free survival was 75.5% in 246 node-positive patients operated on during the luteal phase and 63.3% in 190 node-positive patients who had surgery during the follicular phase. The hazard ratio at Cox multivariate analysis was 1.329 for all patients (p = 0.006) and 1.431 for node-positive patients (p = 0.03). In our study, premenopausal patients with breast cancer and positive axillary nodes operated on during the luteal phase had a significantly better prognosis than patients operated on during the follicular phase. It may be that the processes of cell metastases, such as loss of adhesiveness, may be enhanced by high concentrations of unopposed oestrogens or by reduced activity of natural killer cells during the first half of the menstrual cycle.

Adult↗

Postmenopausal endometrial hyperplasia: role of danazol therapy.

OBJECTIVES: To confirm the effectiveness of danazol in the management of simple or complex endometrial hyperplasia without atypical features, as has been demonstrated previously. METHODS: Seventy-six patients affected by postmenopausal histologically-confirmed endometrial hyperplasia with uterine bleeding were submitted to danazol therapy at a dose of 400 mg/day for 3 consecutive months. RESULTS: After cessation of treatment, 82.8% of the patients (63/76 enrolled) showed a conversion of the hyperplasia into atrophic (65.8%), secretory (11.9%) or proliferative (4.2%) endometrium at the histological examination. Uterine bleeding disappeared, during the therapy, in 90% of the responders (59/63). CONCLUSIONS: Although 17.1% of the women had a persistence of the hyperplasia and 8.4% of the symptom-free women relapsed after 4 months of follow-up, this experience confirms the effectiveness of danazol therapy in hyperplastic endometrial lesions. Nevertheless, a study comparing danazol and progestin therapy is required.

Aged↗

Fenretinide (4-HPR) in chemoprevention of oral leukoplakia.

A controlled clinical trial has been underway at the Istituto Nazionale Tumori (INT) of Milan since 1988. The goal of the trial is to evaluate the effectiveness of fenretinide (4-HPR) in preventing relapses, new localizations, and carcinomas in patients with benign postoperative diagnoses who have been surgically treated for oral leukoplakias. This paper presents the design and the preliminary results of this study. To date, 137 patients have been randomized, following surgical excision of oral leukoplakia, to receive either 200 mg 4-HPR daily for 52 weeks or no intervention. Twenty local relapses or new localizations have occurred so far in the control group and 9 in the 4-HPR group. Seven patients have interrupted the intervention because of toxicity. No impaired dark adaptation has been observed. We conclude that 4-HPR is well-tolerated and appears to be effective in preventing relapses and new localizations during the treatment period.

Adult↗

Mutations of the p53 tumor suppressor gene in neoplasms of the human nervous system.

A variety of neoplasms of the human nervous system were analyzed for the presence of mutations in the p53 tumor suppressor gene. DNA was extracted from frozen or formalin-fixed, paraffin-embedded material. Single-strand conformation polymorphism (SSCP) analysis for exons 5-8 was followed by direct DNA sequencing. Mutations leading to an amino acid change were found in three of 11 (27%) low-grade (World Health Organization (WHO) Grade II) astrocytomas. They were located in codon 183 (TCA-->TGA) of exon 5, codon 237 (ATG-->ATA) of exon 7, and codon 273 (CGT-->CAT) of exon 8. In one of these cases, the sequence indicated loss of the wild-type allele. Of 12 juvenile pilocytic astrocytomas (WHO Grade I), none contained a p53 mutation, suggesting a different molecular basis for this childhood neoplasm. Except for a mutation in one of seven (14%) meningeal hemangiopericytomas (codon 238; TGT-->TTT, Cys-->Phe), no mutations were observed in exons 5-8 of the p53 gene in any of the following tumors of the nervous system and its coverings: 13 schwannomas, 12 central neurocytomas, 22 meningiomas, 10 choroid plexus papillomas and carcinomas, and 30 neuroblastomas of the sympathetic nervous system. These and published data support the view that p53 mutations are frequently involved both in low-grade and progressive (anaplastic) astrocytomas, including glioblastomas multiforme. Oligodendrogliomas, medulloblastomas, meningiomas, and hemangiopericytomas rarely (< 15%) show p53 mutations in exons 5-8, whereas none of the remaining nervous system neoplasms revealed evidence of an involvement of the p53 gene in their development.

Adolescent↗

Natural interferon-beta treatment and steroid hormone receptors in primary endometrial cancer.

Forty-three patients with primary endometrial carcinoma were treated with natural interferon-beta (IFN-beta) at two different dose levels (2 x 10(6) IU or 6 x 10(6) IU im 3 times/week for 1 week). IFN-beta increased receptors for estrogens (ER) and progesterone (PR) in a high percentage of the 40 evaluable patients, without modifying the receptor affinity. The ER and PR enhancement, which was simultaneous in at least 50% of patients, and the increase of over 100 fmol/mg protein observed in some cases suggest that IFN-beta exerts a profound influence on receptor expression and, probably, on the hormone sensitivity of the tumor.

Adenocarcinoma↗

Cervical carcinoma in young patients: clinical and pathological variables.

Twenty-five (10.2%) out of 243 untreated patients with invasive cervical carcinoma were 35 years old or younger. When matching the clinical and pathological variables between the younger and the older women, the former were characterized by a higher rate of Stage IB disease (P = 0.10), G3 and G4 tumors (P = 0.25), bulky lesions (P = 0.05) and node metastases (P = 0.50). In spite of this poorer pathological profile, both the 5-year disease-free survival rate (75%) and survival according to stage of the younger women were similar to those reported in larger series, regardless of the patients' age. No modification of the standard therapy is therefore required in younger patients.

Adult↗

Analysis of electroporation-induced genetic damages in V79/AP4 Chinese hamster cells.

Electroporation is a recent technique used to introduce exogenous DNA into eukaryotic cells. It is important to establish that the gene of interest is transferred into a functional, non-mutated recipient cell. V79/AP4 Chinese hamster cells were exposed to high-voltage pulsed electric fields and some biological and genetic effects were measured. The results showed that cytotoxicity was related in a dose-dependent manner to the number of applied pulses. Thioguanine-resistant colony-forming cells as well as chromosomal aberrations were also induced whereas ouabain resistants and sister-chromatid exchanges were not or slightly induced. Spontaneous and electroporation-induced clones that were phenotypically TGR/HATS were used to investigate the hprt locus. Molecular screening of the locus showed that the number of deleted exons was significantly higher in induced than in spontaneous TG-resistant clones, suggesting that the genetic damages induced by electroporation concern the loss of regions well over the size of the hprt locus.

Animals↗

[Paraneoplastic erythema associated with a carcinoma of the cervix. Our experience].

The authors report a case of bullous erythema observed in a young woman affected with II B stage carcinoma of the cervix, whose clinical course was likely to be a paraneoplastic lesion. The aim of the report is to outline such a rare association between a dermatologic pattern and a gynecologic tumor and to synthesize the literature's data concerning this matter.

Adult↗

[Amlodipine in isolated systolic hypertension in the aged].

The authors studied the efficacy and safety of a long half-life dihydropyridine calcium-antagonist--amlodipine--in a single daily dose in the treatment of isolated systolic hypertension in the elderly. Ninety-seven subjects, age range 65-85 years, with isolated systolic hypertension were randomized into two groups, similar for age, weight and height, of 47 subjects submitted to active therapy and 50 subjects to placebo, respectively. The study was divided into two phases: in the first one, of three weeks, the first group was administered amlodipine at the dose of 5 mg/day; in the second period, which lasted 9 weeks also in case of systolic pressure normalization, amlodipine at the dose of 10 mg/day was administered. Forty-one subjects of the active drug group and 41 of the control group completed the study. The results were determined as mean +/- standard deviation; statistical analysis was completed by the Student T test. In the amlodipine group, at the end of the third week, a significant decrease in systolic arterial pressure was reported; at the end of the follow-up a further decrease in systolic arterial pressure was observed in the active treatment group as compared to the control group (p < 0.001). The other parameters considered (E.C.G., routine haematochemical tests) did not show significant changes in the two groups during the whole study period. Furthermore, during the follow-up, neither orthostatic hypotension nor reflex tachycardia, events which require particular attention during antihypertensive therapy in the elderly, were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Radiotherapy for vulvar carcinoma with positive inguinal nodes. Adjunctive treatment.

Between 1981 and 1988, 58 patients with vulvar carcinoma underwent radical vulvectomy and unilateral inguinal lymphadenectomy. Sixteen patients with inguinal node metastases received complementary radiotherapy as an alternative to pelvic node dissection. They were treated with Co-60 therapy for bilateral inguinal and pelvic lymph nodes. The overall five-year actuarial survival rate in patients without node involvement was 84%; in patients with positive inguinal nodes treated with the combined radiosurgical approach, it was 64%. Patients with 1 node involved had a 74% rate of estimated survival, and those with 2 or more metastatic nodes, considered to be at high risk, had an estimated survival rate of 49%. Only mild to moderate side effects related to the radiation therapy were observed, and in no case was it necessary to interrupt the treatment. In terms of survival, the results obtained in the group of patients with postoperative radiotherapy were better than those normally expected after pelvic lymphadenectomy, and as suggested in recent literature, point to the promising role of irradiation as adjuvant management for vulvar cancer with node involvement.

Actuarial Analysis↗

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↗