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Biomedical subjects

M Greco

Publications and source records attributed to M Greco.

At least 73 records · Page 4Linked to original sources
PubMed1998

Impact of the diagnostic methods on the therapeutic strategies.

Over the last 25 years the diagnostic approaches and therapeutic strategies of breast cancer have dramatically changed. The relationship between diagnosis and therapy has gradually become more complex due to the ever more sophisticated diagnostic tools (mammographic screening, digital mammography, magnetic resonance, SPECT scan and FDG-PET), which have improved resolution limits and accuracy, and also due to the different therapeutic planning applied to breast cancer in these years (conservative surgery, neo-adjuvant chemotherapy, axillary dissection or not). Thus, in this paper, we have briefly analyzed the many open questions in breast cancer management and the clinical challenges of present diagnostic tools in relation to pre-, peri- and postoperative phases, and to therapeutic strategies in general. The main goal of mammographic screening is to detect early invasive cancers and to treat them at the first useful moment. However, at which age should one begin screening, and what is the impact on overall survival, the cost-effectiveness, and, most of all, the best operative approach to suspect lesions? Can digital mammography give a better quality of imaging with respect to conventional mammography? Does unexpected multicentricity and/or multifocality, which is sometimes showed by magnetic resonance, have any clinical relevance? Is this technique really better than traditional methods for the identification of local recurrence? Is scintimammography able to improve the low diagnostic accuracy of mammography on non-palpable breast lesions? Moreover, at present, the need for axillary dissection and its therapeutic and staging value is deeply debated: however, clinical detection of axillary metastases is not a reliable diagnostic tool and there are no conventional radiologic techniques to be used: recently nuclear medicine imaging has provided various approaches, such as SPECT scan with different tracers, FDG-PET, or lymphoscintigraphy with gamma probe sentinel biopsy: there are not only methodologic but also phylosophic differences in using these techniques. Neo-adjuvant chemotherapy has allowed a dramatic reduction of primary breast cancer with a replanning of the surgical approach to large breast tumours but, at the same time, has posed new questions such as the adequacy of diagnostic pre- and perioperative revaluation. Finally, does postoperative follow-up take advantage of intensive diagnostic programs and are there therapeutic margins which would improve survival of patients with metastatic disease? This paper is an attempt to analyze the answers given in the literature. Nevertheless, at present, this matter is globally in progress and a scientific debate will provide, in the near future, a new promising scenario for breast cancer management.

Age Factors↗
PubMed1997

Breast cancer staging using technetium-99m sestamibi and indium-111 pentetreotide single-photon emission tomography.

We evaluated the clinical usefulness of single-photon emission tomography (SPET) with technetium-99m sestamibi and indium-111 pentetreotide in breast cancer staging. Fifteen patients with clinical and/or mammographic findings suggesting T1-2N0-1 breast cancer were studied. SPET images were acquired 20 min after 99mTc-sestamibi injection and 4 and 24 h after 111In-pentetreotide injection. Patients underwent surgery the day after the later 111In-pentetreotide acquisition. Pathological examination showed 16 tumours in the 15 patients, with one bilateral carcinoma. The mean tumour diameter was 18.7 mm. Metastatic axillary involvement was found in 6/16 tumours, with a mean of five metastatic nodes per axilla. Both tracers correctly identified 15/16 primary tumours and five of the six cases of metastatic axillary node involvement. No difference between the tracers was observed in breast cancer staging. 99mTc-sestamibi seems to be the better tracer in terms of physical characteristics, execution time and cost-effectiveness. Our data suggest the future possibility of using nuclear medicine imaging to avoid axillary dissection in patients with T1 breast cancer.

Axilla↗
PubMed1997

The minimal effective exemestane dose for endocrine activity in advanced breast cancer.

Phase I studies have demonstrated that exemestane, an irreversible oral aromatase inhibitor, is able to suppress circulating oestrogen levels. In our previous experience, doses ranging from 2.5 to 25 mg induced a similar suppression of oestrogens. The aim of this study was to identify the minimum effective exemestane dose on the basis of endocrine activity. 20 evaluable postmenopausal advanced breast cancer patients were randomly given exemestane 0.5, 1, 2.5 or 5 mg, in double-blind conditions. Oestrone (E1), oestradiol (E2), oestrone sulphate (E1S), gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate serum levels were evaluated from the first day of treatment to the 7th, 14th, 28th and 56th day. Serum E1, E2 and E1S levels were suppressed by all doses starting from day 7; the degree of inhibition versus baseline was 25 up to 72% for E1, 30 up to 62% for E2 and 16 up to 52% for E1S, with higher doses achieving greater suppression; these changes were maintained over time. A significant increase in FSH and LH levels was observed for all doses. Treatment tolerability was satisfactory. The endocrine effects of exemestane appear to be dose related and 0.5 and 1 mg are ineffective for adequately suppressing circulating oestrogens.

Aged↗
PubMed1997

The irradiation of hepatocytes with He-Ne laser causes an increase of cytosolic free calcium concentration and an increase of cell membrane potential, correlated with it, both increases taking place in an oscillatory manner.

Isolated hepatocytes were irradiated with Helium-Neon laser (fluence: 0.24 Joules x cm-2, fluence rate: 12 mW x cm-2) and changes of both cytosolic free Ca2+ concentration and cell membrane potential were checked by measuring fura-2 and bis-oxonol fluorescence respectively. Irradiation resulted in an enhancement in cytosolic free Ca2+ concentration that requires the presence of Ca2+ in the phase outside hepatocytes; consistently an increase in cell membrane potential was measured correlated with it. Interestingly, the rate of increase of both cytosolic free Ca2+ concentration and cell membrane potential shows special time dependent features similar to those peculiar of oscillatory processes.

Animals↗
PubMed1997

Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five-year results.

PURPOSE: To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS: Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS: Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION: HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.

Adult↗
PubMed1997

Pilot study of primary chemotherapy with doxorubicin plus paclitaxel in women with locally advanced or operable breast cancer.

A pilot study of primary chemotherapy with bolus doxorubicin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infused over 3 hours was performed in 38 women with locally advanced and 41 with stage II/III breast cancer. Patients received four cycles of primary chemotherapy followed by surgery and treatment with cyclophosphamide/methotrexate/5-fluorouracil for six cycles. Preliminary data are available on 73 patients. Doxorubicin plus paclitaxel was well tolerated. Primary toxicity consisted of grade 1 or 2 reversible peripheral neuropathy and grade 3 alopecia. After a median follow-up of 13 months, none of the patients have developed cardiac toxicity or any significant alteration of the left ventricular ejection fraction, which was measured before treatment, at each cycle of doxorubicin plus paclitaxel, and every 3 months thereafter. Major clinical response of the breast tumor was observed in 88% of patients. At pathologic examination of the surgical specimen, 40% were pT1, 15% had no macroscopic tumor residue, and 7% had complete disappearance of invasive neoplastic cells. After a median follow-up of 17 months for patients with locally advanced breast cancer, freedom from progression was 67%, disease-free survival was 71%, and overall survival was 74%. The same end points were 100% for patients with stage II/III disease, with a shorter median follow-up of 10 months. In conclusion, doxorubicin plus paclitaxel is safe, feasible, and effective, and can be used as primary or adjuvant chemotherapy to assess its actual therapeutic role in women with early breast cancer.

Adult↗
PubMed1996

Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease.

BACKGROUND: Diagnosis of many immune-mediated diseases is helped by detection of antibodies directed against the pathogenetic (self or foreign) antigen. In coeliac disease (CD), we have a situation in which antiendomysial antibodies (EMA), which are not specific for the pathogenetic antigen, reach a specificity and sensitivity of detection of CD approaching 100%, whereas detection of antibodies against gliadin (AGA), the pathogenetic antigen, is far less specific and sensitive in diagnosis. No direct evidence of a relation between gluten/gliadin challenge and EMA production exists. We tried to establish whether the small intestine of CD patients is the site of EMA production and whether gliadin challenge could induce their release. METHODS: Small intestine biopsy samples from treated (23) and untreated (16) CD patients and controls (18) were cultured in vitro for 24-48 h in the presence of gliadin, another alimentary antigen, or medium. EMA and AGA were detected in the supernatants of these organ culture biopsy samples by ELISA and immunofluorescence technique, respectively. FINDINGS: No EMA were found in the culture supernatants of biopsy samples of 18 controls, whereas they were detected in the culture supernatants of all 16 untreated CD patients irrespective of gliadin challenge. Conversely, EMA were not detected in supernatants of biopsy samples cultured in medium only from 23 treated CD patients, but were detected in 17 of the 23 biopsy samples challenged with gliadin. INTERPRETATION: Our results suggest that a more complex pathogenetic mechanism than normally accepted is involved in CD. Furthermore, our findings raise the possibility that EMA, or the antigen recognised by them, are involved directly in the pathogenesis of CD.

Antibody Formation↗
PubMed1996

Right ventricular myocardial function in ARF patients. PEEP as a challenge for the right heart.

OBJECTIVE: To examine the hemodynamic effects of external positive end-expiratory pressure (PEEP) on right ventricular (RV) function in acute respiratory failure (ARF) patients. DESIGN: Prospective, with retrospective analysis on the basis of RV volume response to PEEP. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: 20 mechanically ventilated ARF patients (mean lung injury score = 2.6 +/- 0.45 SD). INTERVENTION: Incremental levels of PEEP (0-5-10-15 cmH2O) were applied and RV hemodynamics were studied by means of a Swan-Ganz catheter with a fast-response thermistor for right ventricular ejection fraction (RVEF) measurement. According to their response to PEEP 15, two groups of patients were defined: group A (9 patients) with unchanged or increased RV end-diastolic volume index (RVEDVI) and group B (11 patients) with decreased RVEDVI. MEASUREMENTS AND RESULTS: At zero PEEP (ZEEP) the hemodynamic parameters of the two groups did not differ. In group A, cardiac index (CI) and stroke volume index (SI) decreased at all PEEP levels (5, 10, and 15 cmH2O), while RVEF started to decrease only at a PEEP of 10 cmH2O (-10.8%), and RVES(systolic)VI increased only at PEEP 15 cmH2O (+21.5%). RVEDVI was not affected by PEEP. In group B, CI and SI decreased at all PEEP levels (5, 10, and 15 cmH2O). Similarly, RVEDVI started to decrease at PEEP 5 cmH2O, while RVESVI decreased only at PEEP 15 cmH2O (-21.4%). RVEF was not affected by PEEP in this group. In each patient the slope of the relationship between RVEDVI and right ventricular stroke work index (RVSWI), expressing RV myocardial performance, was studied. This relationship was significant (no change in RV contractility) in 8 of 11 patients in group B and in only 2 patients in group A. In 4 patients in group A, PEEP shifted the RVSWI/RVEDVI ratio rightward in the plot, indicating a decrease in RV myocardial performance in these patients. CONCLUSIONS: PEEP affects RV function in ARF patients. The decrease in cardiac output is more often associated with a preload decrease and no change in RV contractility. On the other hand, the finding of increased RV volumes with PEEP may be associated with a reduction in RV myocardial performance. Thus, these results suggest that assessment of RV function by PEEP and preload recruitable stroke work may disclose otherwise unpredictable alterations in RV function.

Adult↗
PubMed1996

Angiotensin-converting enzyme activity in stools of healthy subjects and patients with celiac disease.

Angiotensin-converting enzyme (ACE) is a dipeptidylcarboxypeptidase that occurs in three types of cells: endothelial, epithelial, and neuroepithelial. ACE activity is present in plasma, urine, and vascular endothelium. High levels of ACE are found in the brush border of human small bowel. The aim of this study was to evaluate ACE activity in human stools and to find a correlation with the intestinal loss of epithelial cells. Fifteen healthy subjects (HS) (8 males, 7 females; age range 6-56 years), 20 patients with celiac disease (CD) (11 males, 9 females; age range 15-53 years), and 18 patients with CD in remission after a gluten-free diet (CD-GFD) (8 males, 10 females; age range 14-54 years) were enrolled in the study. The fecal ACE activity was measured in all groups. Fecal samples were kept at -20 degrees C for a subsequent test. In HS, fecal ACE activity was 21.03 +/- 16.17 nmol/min/100 g (mean +/- SD). In patients with CD with subtotal mucosa atrophy, ACE activity was significantly higher (113 +/- 88.94) than in HS and CD on GFD (36.65 +/- 23.9). We have demonstrated ACE activity in human stools. ACE activity in stools seems to derive from the microvilli of the intestinal mucosa, thus suggesting the potential usefulness of ACE determination as an index of enterocyte damage.

Adolescent↗
PubMed1996

Increase in cytosolic and mitochondrial protein synthesis in rat hepatocytes irradiated in vitro by He-Ne laser.

In order to gain an insight into the mechanism of cell photostimulation by laser light, protein synthesis was measured in hepatocytes irradiated with a low-power, continuous-wave He-Ne laser (fluence, 0.24 J cm(-2); fluence rate, 7 and 12 mW cm(-2)). As a result of irradiation, the rate and amount of 35S-methionine incorporated into newly synthesized proteins increased, as demonstrated by gel electrophoresis and quantitative analysis of labelled protein bands. The stimulation of protein synthesis was fluence dependent, with a maximum stimulation at 0.24 J cm(-2) for both fluence rates (12 and 7 mW cm(-2)). Both cytosolic and mitochondrial protein synthesis increased as a result of irradiation, as demonstrated by the measurement of hepatocytes previously treated with chloramphenicol and cycloheximide respectively. An initial investigation showed that stimulation of protein synthesis also occurred in hepatocytes irradiated with a non-coherent radiation source (fluence, 0.24 J cm(-2)).

Animals↗
PubMed1996

Squamous cell carcinoma of the penis.

Penile tumors, although not frequent, represent a difficult diagnostic and therapeutic challenge. Of the malignant penile neoplasms, the most frequent is penile carcinoma, which includes squamous cell carcinoma and its well-differentiated variant, verrucous carcinoma. Current concepts about classification, epidemiology, pathogenesis, histopathology, diagnosis, staging, prognosis, and treatment are presented.

Carcinoma in Situ↗
PubMed1996

Gluten-sensitive disease with mild enteropathy.

BACKGROUND & AIMS: Celiac disease is a permanent gluten intolerance strongly associated with HLA class II antigens and possibly showing milder changes of mucosal architecture. Ten patients with symptoms suggesting celiac disease and serum antiendomysium antibodies with normal mucosal architecture were studied. METHODS: Immunohistochemical detection of mucosal immune activation and HLA typings were performed. RESULTS: Mucosal immune activation, with normal mucosal architecture and normal gamma/delta+ intraepithelial lymphocytes counts, was found on a gluten-containing diet. In 3 of 6 patients, multiple biopsy specimens showed one sample with severe villous atrophy. Clinical and immunomorphologic features were strictly gluten dependent. The mucosal immune activation was elicited in vitro by gliadin. Only 4 patients had the typical HLA typing of celiac disease. CONCLUSIONS: Gluten-sensitive celiac-like symptoms may occur in patients with serum antiendomysium antibodies, apparently normal intestinal mucosa, and HLA typing not commonly associated with celiac disease. These patients should undergo multiple biopsies, and signs of immunologic activation should be sought accurately; in the presence of mucosal immune activation, a trial with a gluten-free diet should be encouraged to detect gluten dependency. In vitro immunologic response of small intestinal mucosa to gliadin may support the diagnosis of gluten-sensitive enteropathy.

Adult↗
PubMed1996

A subnecrogenic dose of diethylnitrosamine is able to initiate hepatocarcinogenesis in the rat when coupled with fasting/refeeding.

Caloric restriction causes a generalized decrease in growth rate and has been repeatedly associated with an inhibitory effect on cancer development in several systems. In contrast, exposure to complete fasting followed by refeeding is a metabolic condition associated with increased cell turnover in different organs, including the liver. The present study examines whether such condition is able to sustain the induction of initiated hepatocytes following a subnecrogenic dose of diethylnitrosamine (DENA). Male Fisher-344 rats were fasted for 4 days and 1 day after refeeding they were given a single dose of DENA (20 or 200 mg/kg body wt, i.p.). Negative and positive control groups were fed ad libitum and injected with 20 and 200 mg/kg of DENA, respectively. One week later all animals were subjected to the resistant hepatocyte model for the selection of hepatocyte nodules and they were killed 2 weeks thereafter. Results indicated the presence of gamma-glutamyltransferase (GGT) positive foci and nodules (38 +/- 7/cm2) in rats regularly fed and given 200 mg/kg of DENA, while virtually no focal lesions (< 1/cm2) were found in the group receiving 20 mg/kg of DENA and fed throughout the experiment. However, a significant number of GGT positive foci/nodules (14 +/- 7) also developed in rats exposed to fasting and given 20 mg/kg of DENA 24 h after refeeding. No evidence of hepatocellular necrosis was found in the latter group following DENA administration. No effect of fasting was observed when rats received 200 mg/kg of DENA. It is concluded that fasting/refeeding provides conditions which are able to sustain initiation in rat liver by a subnecrogenic dose of a carcinogen. These findings are in contrast with the commonly reported inhibitory effect of chronic food restriction on various stages of carcinogenesis, including initiation.

Animals↗
PubMed1996

Can provocative growth hormone testing predict the response to recombinant human growth hormone (rhGH) treatment?

Treatment with rhGH has been proven to be useful in children with chronic renal insufficiency and stunted growth. The aim of this study was to assess the usefulness of endocrinological provocative testing in predicting results to rhGH treatment. Endocrinological investigations performed in 14 children on renal replacement therapy did not correlate with increment of height velocity in the first year of rhGH therapy. It is concluded that no endocrinological testing is useful before starting rhGH treatment; other predictors of the response to rhGH administration are needed.

Adolescent↗
PubMed1996

[Tuberculosis and immigrants. A study of its prevalence in the Umbria region].

In 1995, 463 patients were admitted in the medical service of Perugia (Sanitary District n. 6). Only 20% of them were enrolled in the TBC programme. Mantoux was: < 10 mm in 35%, 10-15 mm in 25%, > 15 mm in 40%. Chest Rx in 30 subjects demonstrated: normality in 19; old TBC in 7, active TBC in 4 (miliary, bilateral upper lobe pneumonitis, left subapical upper lobe pneumonitis and right lobitis of the upper lobe). All patients were admitted in hospital and showed positive sputum culture for Mycobacterium Tuberculosis. They were treated with isoniazid, rifampin, pyrazinamide, ethambutol/streptomycin for 2 months and with isoniazid, rifampin for other 4-8 months. Two patients showed Mycobacterium tuberculosis with isoniazid resistance. Seven patients were treated with isoniazid chemoprophylaxis without side effects. Migrants should receive information about health care service and be encourage to register themselves with a general practitioner. Skin test screening and chest radiographs for those with positive results should be provided at a convenient location.

Adolescent↗