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Biomedical subjects

M Greco

Publications and source records attributed to M Greco.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Intestinal occlusion caused by an intramural ileo-cecal-colonic hematoma during treatment with oral anticoagulants].

The Authors report a case of bowel occlusion due to intramural ileocecocolic haematoma in a patient in treatment with oral anticoagulants. This case is interesting both to unusual etiology correlated to the localization and because there are many concomitant pathogenetic factors; this case was treated on urgency by bowel resection and it had a good prognosis. The Authors discuss the diagnostic and therapeutic difficulties and conclude that in patients with anticoagulant oral therapy an accurate clinical follow-up is required.

Aged↗
PubMed2000

[Simultaneous detection and typing of human papillomavirus in cervical biopsies using PCR-reverse hybridization].

INTRODUCTION: Genotyping of Human papillomavirus (HPV) is an important step in the clinical evaluation of the oncogenic risk associated with HPV infection of cervical mucosa. The purpose of this work was to develop a fast PCR-reverse-hybridization assay (PCR-RH) for the simultaneous detection and genotyping of anogenital HPVs. METHODS: HPV DNA from cervical biopsies was amplified by consensus primer-PCR. Digoxigenin-labeled PCR products were hybridized to type-specific probes anchored to the surface of plastic microwells and revealed by an ELISA system. RESULTS: The method was tested on 115 clinical samples (81 koilocytic atypias, 11 CIN1, 10 CIN2, 12 CIN3 and 1 squamous carcinoma). HPV DNA was found in 56.7% koilocytic atypias, in 90.9% of CIN1 and in 100% of CIN2 and higher-grade lesions. Thus, PCR-RH is sensitive, rapid, easy-to-perform and readily applicable to the routine analysis of a large number of samples.

Biopsy↗
PubMed1999

Fluctuation of HER2 expression in breast carcinomas during the menstrual cycle.

The hormonal milieu at time of tumor surgery seems to have a significant impact on survival in premenopausal breast cancer patients. Indeed, surgery performed during the follicular phase of the menstrual cycle was suggested to correlate with a poor prognosis. To investigate the relationship between prognosis and menstrual cycle at time of surgery, we analyzed the expression of some markers associated with tumor aggressiveness, such as the hormone receptors, HER2, p53, Bcl2, and cathepsin D in breast carcinomas obtained from 198 premenopausal women who underwent surgery during different phases of the menstrual cycle. HER2 overexpression was found to fluctuate in hormone receptor-positive tumors. In actual fact, 20% of the tumors removed during the follicular phase scored HER2-positive, versus 8% of those removed during the luteal phase. Similarly, a number of hormone receptor-positive tumor specimens, obtained from the same patients during follicular and luteal phases, were scored HER2-positive when the sample was removed during the follicular phase and HER2-negative when removed in the luteal phase. Southern blot analysis of the HER2 gene indicated that, in hormone receptor-positive cases, the overexpression of HER2 is often not associated with gene amplification. The finding that overexpression of the HER2 gene, associated with tumor aggressiveness, can fluctuate according to the hormonal milieu may explain the increased survival of patients operated during the luteal phase. It is also relevant to the selection and treatment of patients most likely to benefit from anti-HER2 antibody therapy.

Adult↗
PubMed1999

Fasting-induced apoptosis in rat liver is blocked by cycloheximide.

The effect of cycloheximide (CH) on the fasting-induced changes of rat liver cell and protein turnover has been investigated. Late starvation phase (3-4-day-fasting period) was characterised by a decrease in liver weight and protein and DNA content. The loss of DNA was not related to liver cell necrosis but due not only to depression of cell proliferation as shown by the drop in the labelling index but also induction of apoptosis. This type of apoptosis was documented by the increase in the apoptotic index (cells labelled by TUNEL) and transglutaminase activity as well as by DNA fragmentation. The liver cells of fasted rats appeared smaller as shown by the higher cell density and DNA/protein ratio than in controls. Females were more resistant to fasting-induced apoptosis than males. A single dose of CH, a drug primary known as inhibitor of protein synthesis, induced or enhanced apoptosis in fed and 2-days fasted male rats, respectively, without any sign of cell necrosis. On the contrary, the administration of repeated doses of CH blocked apoptosis induced by fasting. CH "froze" protein and DNA content as well as apoptotic process at the level of 2 days-fasted rats. While fasting-induced liver protein loss resulted from a marked reduction in protein synthesis with a slight decrease in degradation, repeated treatment with CH virtually blocked protein loss by abolishing protein catabolism. These data suggest a direct relationship between the catabolic side of protein turnover and the apoptotic process.

Animals↗
PubMed1999

Periodic breathing during sleep in patients affected by fibromyalgia syndrome.

Seventeen patients affected by fibromyalgia syndrome (FMS) (16 females and one male) and 17 matched healthy subjects underwent formal polysomnography, a sleep questionnaire and lung function tests. FMS patients slept significantly less efficiently than the healthy controls (p<0.01), had a higher proportion of stage 1 sleep (mean+/-SD, 21+/-6% versus 11+/-4%; p<0.001), less slow wave sleep (p<0.01) and twice as many arousals per hour of sleep (p<0.001). The respiratory pattern of FMS patients showed a high occurrence of periodic breathing (PB) (15+/-8% of total sleep time) in 15/17 patients, versus 2/17 control subjects. The short length of apnoeas and hypopnoeas did not affect the apnoea/hypopnoea index (5.1+/-3.5 versus 3.2+/-1.6; NS), but FMS patients had a greater number of desaturations per hour of sleep (8+/-5 versus 3+/-3; p<0.01). Pulmonary volumes did not differ between the two groups, but FMS patients had a lower transfer factor of the lung for carbon monoxide (TL,CO (5.8+1 versus 7.7+1 mmol x min(-1) x kPa(-1); p=0.001). PB occurrence correlated with TL,CO (r=-0.62; p=0.01), number of desaturations (r=0.76, p=0.001) and carbon dioxide tension in arterial blood (Pa,CO2) (r=-0.50; p=0.05). Stepwise multiple linear regression analysis showed desaturation frequency (p=0.0001) and TL,CO (p=0.029) to be the best predictors of PB percentage (R2 0.73; p=0.0001). Patients complaining of daytime hypersomnolence had a higher number of tender points, about twice as many arousals per hour and a lower sleep efficiency than patients who did not report this symptom. TL,CO was more impaired and the occurrence of PB was higher. The occurrence of periodic breathing in fibromyalgia syndrome patients, which was previously unreported, and is shown to be linked to a reduction of transfer factor of the lung for carbon monoxide could play a major role in the symptoms of poor sleep of these patients.

Disorders of Excessive Somnolence↗
PubMed1999

Effect of fasting/refeeding on the incidence of chemically induced hepatocellular carcinoma in the rat.

Caloric restriction has been associated with a delay in the development of both spontaneous and induced neoplasia. In contrast, cycles of fasting/refeeding were shown by us and others to enhance the incidence of early lesions during chemical carcinogenesis in rat liver. The present, long-term study was undertaken to establish whether such a diffential effect would also extend to the later phases of cancer development, until the overt appearance of neoplasia. Male Fischer 344 rats were initiated with a single dose of diethylnitrosamine (DENA, 200 mg/kg i.p.) and starting 1 week later they were either exposed to three cycles of fasting (3 days) followed by refeeding (11 days) or were fed continuously. Seven weeks after DENA administration the rats were exposed to the resistant hepatocyte model of the liver tumor promotion protocol. All animals were killed 1 year after initiation. Incidence of hepatocellular carcinoma was 2-fold higher in the fasted/refed group compared with the controls (72 versus 36%). In addition, cancers were also larger and of higher histological grade in the former group, with one animal showing metastases to the lungs, while no metastases developed in control animals. Fasting caused a decrease in total liver DNA (from 25.2 +/- 1.1 to 16.5 +/- 1.1 mg after 3 days) which was associated with a decrease in hepatocyte labeling index and mitotic activity and high levels of single cell death (apoptosis). In contrast, a sharp increase in hepatocyte proliferation was observed on day 2 of refeeding and this was more pronounced in glutathione S-transferase 7-7 positive foci compared with surrounding liver (10.2 +/- 2.3 versus 4.6 +/- 0.8%). Such a proliferative wave was associated with a sharp decline in the incidence of cell death. It is concluded that fasting/refeeding performed early after initiation accelerates the development of chemically induced hepatocellular carcinoma in the rat.

Animals↗
PubMed1999

Importance of the level of axillary involvement in relation to traditional variables in the prognosis of breast cancer.

Survival in breast cancer correlates with the presence of metastatic lymph nodes, so that removal and pathological examination of the axillary nodes provides the most important prognostic information and basis for planning subsequent therapy. However as the size of primary tumours at diagnosis is decreasing, the likelihood of axillary involvement is also declining, so that the indications for axillary dissection are undergoing radical revision. To definitively establish the value of removing all three axillary lymph node levels (as defined by Berg) in node positive breast cancer, retrospective analysis of a large series receiving complete dissection was carried out. consecutive breast cancer patients (n=1003) with positive axillary nodes were analyzed: all received identical axillary treatment and the three levels were tagged with metal disks to facilitate recognition and pathological examination. Follow-up (mean 97 months) was exceptionally complete. The length of disease-free and overall survival were taken as the primary endpoints. The variables considered in the statistical analysis were tumour size, number of metastatic nodes, axillary invasion by level (the three classic levels), perilymphnodal invasion and age. By univariate analysis, overall and disease-free survival decreased significantly as tumour diameter, number of involved lymph nodes, and involvement by axillary level increased. Multivariate analysis assessing the relative importance of these variables when all were considered together found that they were all important independent predictive factors for survival. This study confirms the importance of tumour size and number of metastatic axillary nodes as predictors of outcome in breast cancer. In addition, the level of axillary invasion as a third independent factor of equal importance to the established indicators was identified. When axillary dissection is performed it should be complete, and all three Berg levels tagged separately, so that involvement by level can be ascertained. This provides additional important prognostic information on which to base subsequent treatment decisions.

Adult↗
PubMed1999

[The indications and controversies for the use of corticosteroids in respiratory deficits in the multiple-trauma patient].

The rational use of corticosteroids in terms of doses, timing and methods of administration, has proved useful in management of the effects of morbidity and mortality in respiratory insufficiency in multiple trauma patients. MPSS (methyl prednisone sodium succinate) is the drug of choice because, compared to other steroids, it penetrates lung tissue more easily (as demonstrated using autoradiographic techniques). The effect of reducing permeability, shown by MPSS, is more marked in the first 6 hours, followed by a progressive diminution. For this reason, it is advisable to administer the drug every 6-8 hours, irrespective of T 1/2 (12-36 h). However, in syndromes of post-traumatic respiratory distress, corticosteroid therapy is only symptomatic, namely it reduces short term mortality, but does not influence the prognosis in the event of persistent microembolism. On the other hand, it is important not to overlook the disadvantages and possible damaging effects linked to the use of corticosteroids in multiple trauma patients. With regard to the use of "alternative" type or support treatments to corticosteroids, the lack of markers documented using atraumatic and reliable techniques hinders the development and clinical application of specific and effective antioxidising treatments. However, alongside the perfection of methods of detecting markers, among the antioxidant drugs, a decisive contribution is expected from the lazaroids or 21-aminosteroids (synthesis steroids). With powerful scavenger activity and antioxidant properties (twice those of MPSS), the lazaroids can provide more suitable solutions to the complex therapeutic problems of these patients, also because they lack glucocorticoid and mineralocorticoid activity.

Adrenal Cortex Hormones↗
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↗