Biomedical subjects

L Mariani

Publications and source records attributed to L Mariani.

At least 127 records · Page 7Linked to original sources

PubMed1996

Diversity among abortion strains of Chlamydia psittaci demonstrated by inclusion morphology, polypeptide profiles and monoclonal antibodies.

Twenty eight C. psittaci abortion strains had been previously classified in to 4 immunologically distinct groups on the basis of cross-protection experiments in a mouse model. To identify the molecular basis of their immunological divergence 4 representative strains were investigated by cellular, molecular and immunological techniques. An identical pattern was obtained by Alul digestion of the amplified major outer membrane protein gene (MOMP) by the polymerase chain reaction (PCR) of the 4 strains. However, inclusion morphology and polypeptide profiles clearly distinguished one strain, named LLG, and its homologous strain POS from the other prototypes by the presence of a unique protein at 26.5 kDa and the absence of a polypeptide at 23 kDa. Six out of 10 monoclonal antibodies (mAbs) raised against abortion strains failed to react with inclusions of the 2 strains. All 6 mAbs reacted with the chlamydial outer membrane complex (COMC). Two of these mAbs, one against the MOMP and one against an antigen at 90 kDa, did not react with immunoblots of LLG and POS. The data provide direct demonstration of the existence of strain variation in the field and classify strains LLG and POS as a distinct C. psittaci serotype 1-subtype. The antigenic diversity among abortion strains should be taken into consideration when designing a subunit vaccine.

Abortion, Veterinary↗

PubMed1996

3-methyladenine-DNA-glycosylase and O6-alkyl guanine-DNA-alkyltransferase activities and sensitivity to alkylating agents in human cancer cell lines.

The activities and the expression of 3-methyladenine glycosylase (3-meAde gly) and O6-alkylguanine-DNA-alkyltransferase (O6 ATase) were investigated in ten human cancer cell lines. Both 3-meAde gly and O6 ATase activities were variable among different cell lines. mRNA levels of the O6 ATase gene, appeared to be related to the content of O6 ATase in different cell lines, whereas no apparent correlation was found between mRNA of 3-meAde gly and the enzyme activity. No correlation was found between the activity of the two enzymes and the sensitivity to alkylating agents of different structures such as CC-1065, tallimustine, dimethylsulphate (DMSO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cis-diamminedichloroplatinum (cDDP) and melphalan (L-PAM). The most striking finding of this study is that a correlation exists between the activity of O6 ATase and 3-meAde gly in the various cell lines investigated (P<0.01), suggesting a common mechanism of regulation of two DNA repair enzymes.

Alkylating Agents↗

PubMed1996

Targeting of O6-methylguanine-DNA methyltransferase (MGMT) activity by antimessenger oligonucleotide sensitizes CHO/Mex+ transfected cells to mitozolomide.

The targeting of mRNA with antisense oligonucleotides is increasingly employed to inhibit the expression of gene function. Since the level of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is decisive in protection of cells against damage produced by alkylating agents, including cytostatic drugs, the targeted inhibition of this repair activity might be of importance for therapeutic approaches. In order to investigate whether antisense targeted MGMT depletion is feasible to transiently modify the sensitivity of cells to anticancer drugs, we studied the expression of MGMT and cellular sensitivity upon inhibitor and antisense treatment using CHO transfectants expressing human MGMT. It was shown by polymerase chain reaction that antisense oligonucleotides specifically inhibited MGMT mRNA level. Nevertheless, MGMT protein was found not to be reduced significantly, as demonstrated by Western blotting. Correspondingly, no significant decrease in MGMT activity was observed, as measured 36 h after MGMT antisense oligonucleotide administration. Given together with the MGMT depleting agent O6-methylguanine, reduction in MGMT protein as well as activity was found. MGMT antisense oligonucleotide enhanced the sensitivity of cells to the tumor therapeutic drug mitozolomide, as measured by sister chromatid exchange formation. This sensitization was further enhanced by combined treatment with antisense oligonucleotide and O6-methylguanine, indicating that MGMT antisense can be supportive in sensitization of cells to an alkylating drug.

Animals↗

PubMed1996

dCTP misincorporation in a Chinese hamster mutator phenotype: the role of GGA genetic context.

Clone CSA7 is a CHEF18 hamster cell line that shows an increased intracellular accumulation of dCTP. To localize the mutations that accumulate spontaneously in a functional gene of such a mutator phenotype, independent CSA7 mutants of the hypoxanthine-guanine phosphoribosyl transferase (hprt) gene were isolated and screened by a polymerase chain reaction-single strand conformation polymorphism technique. Sixty-two percent of mutants produced detectable changes of the strand migration profile and the mutations were preferentially localized in the exons 3 (31%) and 6 (62%). The sequencing of such exons revealed that the rate of C base incorporation was the major mutation pathway and that the A base of a GGA sequence was the preferential site of misincorporation.

Animals↗

PubMed1996

Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease.

PURPOSE: The aim of the study was to evaluate the activity of vinorelbine (VNLB) in a population of advanced ovarian cancer patients, with particular attention to defining its role in platinum-resistant disease. PATIENTS AND METHODS: Thirty-three patients were recruited and treated with VNLB 25 mg/m2 intravenously (IV) weekly. the median age was 53 years, performance status 0 to 2, and number of previous chemotherapy regimens two (range, one to five). Twenty-four patients were platinum-resistant; the remaining nine either were platinum-sensitive (four cases) or had undetermined sensitivity (five cases). RESULTS: The mean delivered dose-intensity of VNLB was 67% of the planned level, because 60% of the cycles were delayed due to neutropenia or anemia. Four partial responses (PRs) and one complete response (CR) were observed, for an overall response rate of 15% (95% exact confidence interval, 5.1% to 31.9%). All the responses occurred in the subgroup of 24 platinum-resistant cases, in whom the response rate was 21% (95% exact confidence interval, 7.1% to 42.1%). Seven patients became stabilized on VNLB, and 27% of the cases showed a reduction in serum cancer antigen 125 (CA 125) levels. G3/G4 side effects consisted of neutropenia, anemia, and worsening of preexisting peripheral neuropathy. No treatment-related deaths occurred. CONCLUSION: VNLB led to a 21% response rate in the population of heavily pretreated and platinum-resistant ovarian cancer patients. Further studies of VNLB alone or in combination with taxanes are warranted in patients with less pretreatment.

Adult↗

PubMed1996

Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma.

Oncogenic rearrangements of RET and NTRK1 proto-oncogenes are frequently detected in papillary thyroid carcinomas. Several studies have shown an association between ionizing radiation and development of this tumor type. In addition in vitro irradiation of tumor cell lines induced rearrangements of RET similar to those observed in human papillary thyroid carcinomas. These two observations could be related to the reported increased incidence of papillary thyroid carcinomas in children living in contaminated areas around Chernobyl, given that it has been demonstrated that about 60% of them presents a RET oncogenic activation. However, this high frequency of RET positivity in radiation exposed children does not rule out the possibility that age could also play a role in the development of RET positive tumors. To assess this possibility we looked for a relationship between the presence of RET and NTRK1 oncogenic rearrangements and age at surgery in a sample of 92 consecutive patients. Our results show that, in papillary thyroid carcinoma, the frequency of RET and NTRK1 activation is significantly higher in the group of patients aged 4-30 years, thas supporting the concept that age could be contributing to this thyroid specific carcinogenic process.

3T3 Cells↗

PubMed1996

[The assessment of the operative risk in vascular surgery].

Atherosclerosis is a polydistrectual disease. The patients with peripheral, carotid or aortoiliac pathology suffer frequently from coronary disease; so, a careful evaluation of operative risk is indispensable related to the anatomic district that we intend submit to surgery. In this work we separately explore the risk related to peripheral revasculations, aortic surgery and carotid surgery following the current literature and our experience.

Aorta↗

PubMed1996

[Disease states and changes in drug pharmacokinetics].

Given that pharmacokinetic data are mostly derived from studies in animals and healthy subjects, the authors highlight how diseases can modify one or more of its phases: absorption, distribution, metabolism and elimination (ADME). Although theoretically all diseases can modify these phases, the authors believe it worth and relevant to focus the discussion on major diseases for which information is available and which are frequent in the population and with the potential to affect more phases, i.e. cardiac, hepatic and renal failure. Therefore, the aim of the paper is to update the data available and to remind that the incidence of adverse reactions to drugs due to changes in their pharmacokinetics is frequent and often serious in these diseases.

Heart Diseases↗

PubMed1996

[Is the placebo still ethically acceptable and scientifically useful in clinical drug experimentation?].

Here, the authors address the question whether the administration of placebo, in clinical trials of drugs to be registered or already registered, is ethically acceptable and/or scientifically useful. An important issue, particularly in view of the different opinions emerging in the international scientific community. Since many diseases are already treatable with established therapies and drugs, clinical trials should be performed mainly with placebo containing the appropriate active compound, in agreement with the Helsinki declaration. Active placebo should be employed when slightly modified compounds are tested and when trials are in phase 2/b, 3 or 4. The use of active placebo in these settings would be more correct from a scientific, ethical and economical point of view.

Clinical Trials as Topic↗

PubMed1996

[Drug surveillance and adverse reactions to drugs. The literature and importance of historical data].

The authors highlight the essential role of pharmacovigilance and the need for a simple, efficient and low-cost system of adverse reaction (AR) reporting which could cover the whole population and all marketed drugs, and suggest that the only one presently viable is based on spontaneous reporting. To support their proposal the authors provide a definition of AR and of the different monitoring system, and list as many drugs as possible to find in the literature that have been associated with a specific AR, together with the active molecule, the therapeutic indication, the features of the AR and the regulatory actions (withdrawal from the market, restriction of use). Moreover, by describing the "history" behind some of these drugs the authors highlight the contribution that pharmacovigilance and spontaneous reporting have had to the development of regulations for approval and marketing of new drugs. It is also highlighted how some of these unexpected events (thalidomide, DES) have had a significant and important contribution to pharmacological and toxicological knowledge.

Dose-Response Relationship, Drug↗

PubMed1995

The influence of radiotherapy on cosmetic outcome after breast conservative surgery.

PURPOSE: The influence of radiotherapy in the cosmetic outcome after conservative surgery for breast cancer was evaluated using an objective method of calculating the asymmetry between the two breasts. METHODS AND MATERIALS: One hundred and one patients treated with the same conservative surgery were evaluated for cosmetic outcome. Sixty-one of them received external radiotherapy (50 + 10 Gy) to the residual breast; the remaining 40 underwent surgery only. The aspect of the patients' breasts was objectively assessed for symmetry by means of a computerized technique. A subjective assessment of the cosmetic outcome was performed both by physician and patient. These objective and subjective assessments were compared in the two groups treated with or without radiotherapy. RESULTS: The results obtained did not show significant differences in terms of cosmetic outcome in the two groups. Skin telangectasia was noted in two radiotherapy patients, while hypertrophic breast scars were only noted in six nonirradiated patients. CONCLUSIONS: We found that standard radiotherapy does not seem to influence the symmetry and the cosmetic results in breast conservative treatment when compared to a similar group of patients with the same quadrantectomy procedure and no radiotherapy.

Adult↗

PubMed1995

Evaluation of second generation CA 125 assays.

OBJECTIVE: This study was performed in order to evaluate and compare the serum CA 125 values obtained using an immunoradiometric (IRMA-II) and an immunoenzymatic (ETI-II) second generation assay, and to establish whether or not the two methods may be used interchangeably. STUDY DESIGN: Serum CA 125 levels were measured in parallel using IRMA-II and ETI-II CA 125 assays (Sorin Biomedica), in 82 women with benign or malignant gynecological diseases. Statistical analysis was performed by linear regression analysis and Wilcoxon's test. RESULTS: Serum CA 125 levels measured using the immunoenzymatic method were lower than those obtained by the immunoradiometric assay. The largest discrepancies between the two methods were found at concentrations of 35-100 U/ml, within which fall cutoff values for the immunoradiometric assay. The cutoff values of 35 or 65 U/ml, frequently used in the original immunoradiometric assay and retained for the immunoradiometric second generation assay, corresponded to 18 and 47 U/ml in the immunoenzymatic second generation assay. CONCLUSION: The discrepancies in CA 125 results obtained by the two detection methods imply that the cutoff values used in the immunoenzymatic procedure should have a lower reference value in order to eliminate high rates of false negative results. Furthermore, their interchangeable use should be avoided in the monitoring of ovarian cancer and other gynecological diseases.

CA-125 Antigen↗

PubMed1995

Breast conservation is a safe method in patients with small cancer of the breast. Long-term results of three randomised trials on 1,973 patients.

Breast conservation has become well-established in the treatment of early mammary carcinoma. However, a standardised treatment modality has not emerged. We have analysed the data from 1,973 patients treated in three consecutive randomised trials by four different radiosurgical procedures: Halsted mastectomy, quadrantectomy plus radiotherapy, lumpectomy plus radiotherapy, and quadrantectomy without radiotherapy, to compare the outcomes of these procedures in terms of local recurrence rate and overall survival. Eligibility criteria were similar in the three trials, and comparability between the four subgroups was excellent. Median follow-up for all patients was 82 months. The annual rates of local recurrence varied markedly according to the treatment. Patients treated with Halsted mastectomy and quadrantectomy plus radiotherapy had low annual rates of local recurrence (0.20 and 0.46, respectively) while both lumpectomy plus radiotherapy and quadrantectomy without radiotherapy had significantly higher rates (2.45 and 3.28, respectively). Patients under 45 years of age had a much higher incidence of local recurrences, while in women over 55 years local recurrences were much less frequent. Overall survival curves were identical in the four groups of patients, so that the three breast conserving radiosurgical procedures had the same survival rates as Halsted mastectomy. However, local recurrence rates were markedly influenced by the treatment method, patient age and specific histological features.

Adult↗

PubMed1995

An I.T.M.O. group study on second-line treatment in advanced epithelial ovarian cancer: an attempt to identify clinical and biological factors determining prognosis.

The aim of the present study was to determine the activity of a combined regimen of mitoxantrone (DHAD) and ifosfamide (IFO) and identify clinical and biological factors with prognostic importance for the second-line treatment of ovarian cancer. The following factors were investigated for their prognostic importance: age, disease sites, platinum responsiveness, histological grade, the presence of clinically/radiologically detectable versus not detectable disease, residual disease volume after first surgery, p53 protein, c-erbB-2 oncoprotein and laminin receptor. 72 patients entered the trial. DHAD and IFO therapy led to a 15% response rate among the 47 cases with clinically/radiologically detectable disease (1 complete and 6 partial responses), with a median response duration of 4 months. The response rate was significantly different according to platinum responsiveness (4% objective responses in platinum-resistant versus 27% in platinum-sensitive disease). The time to treatment failure (TTF) and overall survival (OS) were affected by the presence of clinically detectable disease at study entry (median TTF 4 months in the presence of clinically/radiologically detectable disease versus 9 months if the disease was not similarly detectable, P = 0.02; median OS 10 months versus 21 months, P = 0.01). Initially overexpressed in only a few tumours, the c-erbB-2 oncoprotein became overexpressed in 36% of platinum-resistant tumours; this modulation did not occur in platinum-sensitive tumours. Furthermore, laminin receptor was expressed in 77% of platinum-sensitive versus 39% of platinum-resistant patients. There were no differences in p53 protein expression according to drug responsiveness.

Adult↗

PubMed1995

Combination goserelin and tamoxifen therapy in premenopausal advanced breast cancer: a multicentre study by the ITMO group. Italian Trials in Medical Oncology.

It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer.

Adult↗

PubMed1995

Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor.

The androstenedione derivative, exemestane (FCE 24304), is a new orally active irreversible aromatase inhibitor. Fifty-six post-menopausal advanced breast cancer patients entered this study to evaluate the activity of four low exemestane doses in reducing oestrogen levels. The drug's tolerability and clinical efficacy were also assessed. Exemestane was orally administered to four consecutive groups at daily doses of 25, 12.5, 5 and 2.5 mg, and the changes in oestrogen, gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate levels were evaluated. Drug selectivity was studied by measuring 17-hydroxycorticosteroid urinary levels. After 7 days of treatment, mean oestrone and oestradiol levels had decreased by respectively 64% and 65% (a decrease which was maintained over time); in the 2.5 mg group, oestrone sulphate levels also decreased by 74%. Gonadotrophin levels were significantly higher, whereas no changes in the other serum hormone levels or any interference with adrenal synthesis were detected. Treatment tolerability was satisfactory: nausea and dyspepsia were reported in 16% of patients. The overall objective response rate was 18%. In conclusion, exemestane is effective in reducing oestrogen levels at all of the tested doses and shows interesting clinical activity.

Adult↗

PubMed1995

[The role of hysteroscopy in the follow up of post-mastectomy patients undergoing adjuvant therapy with Tamoxifen].

The authors report on up to date knowledge of the risk of endometrial carcinoma women operated on mastectomy for breast carcinoma and treated with TAM. Starting from their own clinical and scientific experience, the authors follow a group of such patients with a strict monitoring, to ascertain the eventual comparison of dysplastic and neoplastic endometrial pathologies. The group numbers 18 patients and the aim of the study is to evaluate the importance of hysteroscopy as a diagnostic approach for this iatrogenic pathology. The authors affirm the validity of this partially invasive diagnostic method that has to be integrated with clinical and laboratory parameters that are justified by the cost/benefit ratio always favourable for the diagnosis of a neoplastic pathology.

Aged↗

PubMed1995

[The audiometric evaluation of Buenos Aires schoolchildren].

This cross-sectional study, which was carried out between 3 May and 30 September 1993, involved examination with a pediatric otoscope of a random sample of 100 first-grade schoolchildren in a Buenos Aires hospital, followed by tonal audiometry and tonal sweep in 90 of those children. The objectives of the study were to discover the frequency of hearing disorders and to evaluate the importance of audiometric screening in the child population. The results were classified according to the type (conduction or perception) and degree (mild, moderate, or severe) of hypoacusis, which was detected in 36 children (39%). Of those affected, 35 had mild or moderate conduction hypoacusis (loss of less than 31 decibels [dB] or less than 41 dB, respectively). No case of severe hypoacusis was found. The authors consider that audiometric screening of children entering primary school is justified by the high frequency of preventable hearing problems and by the repercussions that those problems can have on speech and learning.

Argentina↗