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M Greco

Publications and source records attributed to M Greco.

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

Low reserve of cytochrome c oxidase capacity in vivo in the respiratory chain of a variety of human cell types.

The question of whether and to what extent the in vivo cytochrome c oxidase (COX) capacity in mammalian cells exceeds that required to support respiration is still unresolved. In the present work, to address this question, a newly developed approach for measuring the rate of COX activity, either as an isolated step or as a respiratory chain-integrated step, has been applied to a variety of human cell types, including several tumor-derived semidifferentiated cell lines, as well as specialized cells removed from the organism. KCN titration assays, carried out on intact uncoupled cells, have clearly shown that the COX capacity is in low excess (16-40%) with respect to that required to support the endogenous respiration rate. Furthermore, measurements of O2 consumption rate supported by 0.4 mM tetramethyl-p-phenylenediamine in antimycin-inhibited uncoupled intact cells have given results that are fully consistent with those obtained in the KCN titration experiments. Similarly, KCN titration assays on digitonin-permeabilized cells have revealed a COX capacity that is nearly limiting (7-22% excess) for ADP + glutamate/malate-dependent respiration. The present observations, therefore, substantiate the conclusion that the in vivo control of respiration by COX is much tighter than has been generally assumed on the basis of experiments carried out on isolated mitochondria. This conclusion has important implications for understanding the role of physiological or pathological factors in affecting the COX threshold.

Adenosine Diphosphate↗
PubMed1998

Release of matrix proteins from mitochondria to cytosol during the prereplicative phase of liver regeneration.

70% partial hepatectomy (PH) in the rat causes a release, into the cytosolic fraction, of mitochondrial matrix proteins, namely the mitochondrial isoform of aspartate aminotransferase (mAAT) and malate dehydrogenase (MDH), during the first 24 h after PH, when no growth of the residual liver is observed. After this time interval, the weight of the liver starts to increase and the normal weight is reached at 96 h after PH. This proliferative phase is characterized by a progressive recovery of the normal levels of intramitochondrial activities of mAAT and MDH. Mitochondria isolated at 24 h after PH show a membrane permeabilization to sucrose accompanied by a release of matrix enzymes; both are blocked by cyclosporin A. These results suggest an alteration of mitochondrial membrane integrity, during the prereplicative phase of liver regeneration, with the occurrence of an increased permeability that allows the passage into the cytosol of matrix enzymes.

Animals↗
PubMed1998

Association between [18F]fluorodeoxyglucose uptake and postoperative histopathology, hormone receptor status, thymidine labelling index and p53 in primary breast cancer: a preliminary observation.

To investigate the possible role of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in the prognostic evaluation of primary breast cancer, we studied 86 patients with T1-3 (TNM classification) breast tumours before surgery and compared the tumour FDG uptake, calculated as a standardized uptake value (SUV), with postoperative histopathological findings, steroid hormone receptor status of the tumour, thymidine labelling index (LI) and tissular expression of p53. SUV was significantly higher in infiltrating ductal carcinomas (n = 68; median SUV = 5.6) than in lobular ones (n = 18; median SUV = 3.8), and in grade 3 carcinomas (n = 26; median SUV = 6.2) than in grade 1-2 ones (n = 60; median SUV = 4.9). Moreover, SUV was significantly higher in carcinomas with high levels of p53 (n = 12; median SUV = 9.5) than in those with low levels (n = 48; median SUV = 4.25). By contrast, there was no significant correlation between SUV and the steroid hormone receptor status or LI of tumours. Our data demonstrate that FDG uptake, expressed as SUV, is associated with certain prognostic factors in breast cancer, such as histopathological grading and p53 expression, which can be assessed only by means of postoperative in vitro examinations. Hence, the information provided by FDG-PET is to some extent related to relevant information on tumour biology. The clinical value of these data will have to be confirmed by analysis of the independence of SUV from other prognostic factors by means of a multivariate analysis performed on a larger series of patients with adequate follow-up. If SUV is confirmed as an independent variable, FDG-PET could assume an important role in the determination of appropriate therapeutic strategies for primary breast cancer.

Adult↗
PubMed1998

Validity of diurnal sleep recording performed by an ambulatory device in the diagnosis of obstructive sleep apnoea.

The objective of this study was to compare the results of oxygen desaturations and sleep apnoea during a daytime nap (D) versus nocturnal sleep (N) evaluation, recorded by a portable multichannel monitoring device in patients with a clinical suspicion of obstructive sleep apnoea (OSA). Two polysomnographic studies were performed, by means of the Healthdyne NightWatch System, in 82 subjects (mean age 57.9 years). No difference was found in the apnoea + hypopnoea index (AHI) and mean SaO2 between D and N recordings. At an AHI threshold of 20, in the D recordings, compared to the N ones, the sensitivity was 91% and the specificity 100%. A good correlation was found for AHI and oxygen desaturation index (ODI) between the two experimental conditions (r = 0.89 and 0.79, respectively). Our study shows that D recordings seem to be accurate for OSA diagnosis in the majority of patients with a clinical suspicion of sleep apnoea syndrome.

Female↗
PubMed1998

Real-patient evaluation of communication skills teaching for GP registrars.

BACKGROUND: Five thousand eight hundred and eighty-five patient-completed questionnaires were used to evaluate the effectiveness of an interpersonal skills module designed for a vocational training programme for GPs. OBJECTIVES: It was anticipated that patient-based assessments would detect a significant improvement in the interpersonal skills of GP Registrars who undertook the module. METHOD: A quasi-experimental design using an intervention and control group (comprising 68 GP Registrars) was used to monitor the outcomes of the interpersonal skills module. RESULTS: Patient ratings of interpersonal skills were significantly higher for those GP Registrars who participated in the interpersonal skills module. CONCLUSIONS: Patient-based assessments are a useful evaluation method for assessing the quality of the doctor-patient relationship.

Adult↗
PubMed1998

A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial.

Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom) which has immune modulating properties. We have conducted two phase I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients. Side effects were mainly mild, especially when infusion was carried out over a 30-minute period. In the SFGH study, where administration was over a ten minute period, there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) and there were four patients who discontinued therapy because of side effects. In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptly after the discontinuation of medication, and all of them were relieved within 24 hours. Patients in the study have shown a trend toward increases in CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of lentinan on certain surrogate markers (recognizing that these were small studies), we recommended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trials did not have measurable p24 levels. In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo were marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of 142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in patients on ddI alone (Gordon et al. 1995).

Adjuvants, Immunologic↗
PubMed1998

Prospective evaluation of fluorine-18-FDG PET in presurgical staging of the axilla in breast cancer.

METHODS: The presurgical, noninvasive staging of axillary nodes for metastases was prospectively investigated in 68 patients who were diagnosed with primary breast cancer using PET with 18F-fluorodeoxyglucose (FDG). Four patients had bilateral nodules; therefore, the total number of evaluable cases was 72. Visual analyses of attenuation-corrected PET images and standardized uptake values (SUVs) of FDG uptake in carcinomas were compared with histopathological surgical findings. The SUV distribution differences between carcinomas with and without axillary metastases were evaluated by means of statistical and receiver operating characteristics analyses. RESULTS: PET correctly classified 64 of the 72 cases; four false-positive and four false-negative PET results were found. The overall sensitivity, specificity and accuracy of PET for axillary metastases were 85%, 91% and 89%, respectively. With respect to the clinical axillary stage of the patients (TNM, or tumor-node-metastasis, classification), we obtained the following results: N0 patients, sensitivity = 70%, specificity = 92%, accuracy = 86%; N1a patients, sensitivity = 85.5%, specificity = 100%, accuracy = 95%; and N1b-2 patients, sensitivity = 100%, specificity = 67%, accuracy = 87%. The median SUV in carcinomas with axillary metastases (4.6) was significantly higher than that in carcinomas without metastases (2.9), but there was a great SUV overlap between the two groups (interquartile ranges = 2.7-7.2 and 1.9-4.5, respectively). Analysis of the receiver operating characteristics curve showed that a high sensitivity of SUV in predicting axillary metastases was associated with a very low specificity and vice versa. With the best SUV cutoff value of 2.9, the sensitivity and specificity were 74% and 56%, respectively. CONCLUSION: PET showed good overall diagnostic accuracy in the detection of axillary metastases (86%). The very high accuracy (95%) in N1a patients is of particular importance. False-negative PET findings, however, can be encountered. SUVs of breast carcinoma cannot predict the spread of the disease to the axilla, even if higher values are often associated with axillary metastases. Any decision on the use of PET in the presurgical staging of breast cancer should be incorporated into a more general debate on axillary management. In selected patients with a very low probability of axillary metastases (T1a), in whom axillary surgery can already be avoided according to data from follow-up studies, 18F-FDG PET could be proposed as a noninvasive imaging modality to improve the diagnosis of axillary relapses.

Axilla↗
PubMed1998

Nuclear medicine approaches for detection of axillary lymph node metastases.

In breast cancer patients the detection of axillary lymph node involvement is a very critical issue, in view of the earlier diagnosis of the disease in recent years, and the increased frequency of very small tumors at first presentation. The size of cancer is related to the risk of axillary metastases, and this may affect the prognosis and the therapeutic strategies. Axillary lymph node involvement is generally recognized as an index of distant microdiffusion, and as it affects overall and disease-free survival, represents the basis for adoption of adjuvant chemotherapy. Routine axillary lymph node dissection (ALND) is expensive, and does not benefit about 70% of early breast cancer patients which are node negative (pN-). Today most of these patients have to sustain the potential morbidity and the economic costs of ALND. The clinical approach is known to be an unreliable diagnostic tool, and for the detection of axillary metastases, conventional X-ray techniques are also unable to solve the problem. By contrast, nuclear medicine procedures have revealed a very interesting diagnostic potential in recent years. This paper analyzes the numerous studies conducted in the field of lymph node visualization and the heterogeneity of the published experiences, taking into account the different approaches proposed in the literature: a) imaging with gamma-emitting tumor seeking agents; b) radioimmunoscintigraphy intravenous (i.v.) or by the interstitial route; c) lymphoscintigraphy with colloids and gamma probe sentinel biopsy; d) positron emission tomography (PET). Although it is very difficult to make a definitive statement about the clinical efficacy of all these methods, this paper reports the most important series of patients examined in the literature as well as the author's own experiences. This can serve as the basis for a better understanding of the potential of nuclear medicine procedures, and gives the reader the opportunity to weigh advantages and drawbacks of each method. At present, lymphoscintigraphy with gamma probe sentinel biopsy and FDG-PET are the nuclear medicine approaches with the best diagnostic performance. However, a correct comparison of the methods will not be possible, until their careful assessment in the same patients is performed. In addition, a final statement today should consider also the increasing need to carry out an economic analysis by evaluating the cost-effectiveness of the examinations.

Axilla↗
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↗