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1.
Phys Rev Lett ; 117(7): 070501, 2016 Aug 12.
Article in English | MEDLINE | ID: mdl-27563942

ABSTRACT

We show how to construct a large class of quantum error-correcting codes, known as Calderbank-Steane-Shor codes, from highly entangled cluster states. This becomes a primitive in a protocol that foliates a series of such cluster states into a much larger cluster state, implementing foliated quantum error correction. We exemplify this construction with several familiar quantum error-correction codes and propose a generic method for decoding foliated codes. We numerically evaluate the error-correction performance of a family of finite-rate Calderbank-Steane-Shor codes known as turbo codes, finding that they perform well over moderate depth foliations. Foliated codes have applications for quantum repeaters and fault-tolerant measurement-based quantum computation.

2.
Mucosal Immunol ; 6(2): 427-34, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22990624

ABSTRACT

Cervical and vaginal epithelia are primary barriers against HIV type I (HIV-1) entry during male-to-female transmission. Cervical mucus (CM) is produced by the endocervix and forms a layer locally as well as in the vaginal compartment in the form of cervicovaginal mucus (CVM). To study the potential barrier function of each mucus type during HIV-1 transmission, we quantified HIV-1 mobility in CM and CVM ex vivo using fluorescent microscopy. Virions and 200-nm PEGylated beads were digitally tracked and mean-squared displacement was calculated. The mobility of beads increased significantly in CVM compared with CM, consistent with the known decreased mucin concentration of CVM. Unexpectedly, HIV-1 diffusion was significantly hindered in the same CVM samples in which bead diffusion was unhindered. Inhibition of virus transport was envelope-independent. Our results reveal a previously unknown activity in CVM that is capable of impeding HIV-1 mobility to enhance mucosal barrier function.


Subject(s)
Cervix Mucus/physiology , HIV-1/physiology , Biological Transport , Cell Line , Cervix Mucus/immunology , Cervix Mucus/virology , Facilitated Diffusion , Female , Humans , Hydrogen-Ion Concentration , Male , Semen/physiology , Semen/virology , Virion/physiology
3.
Oncol Rep ; 15(5): 1345-50, 2006 May.
Article in English | MEDLINE | ID: mdl-16596209

ABSTRACT

A dose-finding study was designed to determine the maximum tolerated dose (MTD) of a bimonthly 12-h (10:00 p.m to 10:00 a.m), timed flat infusion (TFI) of 5-fluorouracil (5-FU) plus irinotecan (CPT-11), without leucovorin (LV), for metastatic colorectal carcinoma (CRC). A total of 33 patients were treated. Seven dose levels included a fixed CPT-11 dose of 180 mg/m2 on days 1 and 15 (d(1,15)) and escalating doses of 5-FU 600-1200 mg/m2 on days 1-4 and 15-18 (d(1-4,15-18)). Dose-limiting toxicities (DLTs) were: grade 3-4 non-hematologic, grade 4 hematologic and any toxicity causing a more than a 2-week delay in treatment. The MTD was reached at the seventh dose level. DLTs were observed in 5/8 patients (63%): G3 diarrhea, 2 patients, associated with G3 mucositis in one instance; G4 neutropenia, 2 patients, associated with severe asthenia in 1 patient; G3 hand-foot syndrome, 1 patient. The recommended doses (RDs) were established at the sixth dose level: 5-FU, 1100 mg/m2/d(1-4,15-18); CPT-11 180 mg/m2/d(1,15) [5-FU and CPT-11 dose intensity (DI), 2200 and 90 mg/m2 per week (w), respectively]. At the recommended dose, the DLTs in 38 cycles were: mucositis, 2 cycles (5%); afebrile G4 neutropenia and hand-foot syndrome, 1 cycle (3%). In 24 assessable patients, the overall response rate was 37.5%. The present CPT-11/5-FU schedule is highly tolerable in an outpatient setting using the highest recommended 5-FU dose effective in advanced CRC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Adolescent , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/pathology , Dose-Response Relationship, Drug , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Irinotecan , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Maximum Tolerated Dose , Middle Aged , Time Factors
5.
Br J Cancer ; 91(4): 618-20, 2004 Aug 16.
Article in English | MEDLINE | ID: mdl-15292944

ABSTRACT

A dose-finding study was undertaken to determine the maximum-tolerated dose, and the recommended dose of docetaxel in combination with 12-h timed (22:00-10:00) flat infusion of 5-fluorouracil (5-FU) in metastatic breast cancer patients. This schedule seems to reduce the occurrence of stomatitis of the docetaxel and infusional 5-FU regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Docetaxel , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Maximum Tolerated Dose , Middle Aged , Neoplasm Metastasis , Taxoids/administration & dosage
6.
Ann Oncol ; 15 Suppl 1: I27-I34, 2004.
Article in English | MEDLINE | ID: mdl-15280184

ABSTRACT

Familial breast cancer, whether associated or not with particular other breast cancer features (male, early onset, bilateral breast cancer), determines a wide and variable risk of developing breast cancer in the 'unpatients' (unaffected individuals) of these families, particularly in those harboring a genetic predisposition. The antiestrogen tamoxifen has been proposed in different trials to prevent breast cancer in women at risk. The NSABP-P1 study demonstrated that tamoxifen drastically reduced (by approximately 50%) the incidence of breast cancer in women at risk selected according to the Gail score. The preventive effect was particularly consistent in postmenopausal women and in those showing familial breast cancer (three or more affected patients). BRCA1/BRCA2 (BRCA1/2) gene analysis in women accrued in the NSABP-P1 trial who developed breast cancer showed that tamoxifen chemoprevention reduced breast cancer incidence in BRCA2 carriers. Different chemoprevention trials are ongoing to compare different selective estrogen receptor modulators and aromatase inhibitors with tamoxifen. The Italian Consortium of Hereditary Breast Ovarian Cancer recently developed the Aromasin Prevention Study, a multicenter, double-blind, randomized, placebo-controlled phase III study evaluating the effect of the aromatase inhibitor exemestane for chemoprevention in postmenopausal women carriers of BRCA1/2 genetic predisposition. Women who are postmenopausal unaffected carriers of BRCA1/2 mutations will be selected by participating institutions and randomly assigned to receive either oral exemestane or oral placebo every day for 3 years in order to reduce the incidence of breast cancer. Genetic counseling and the detection of predisposing BRCA1/2 mutations are mandatory before accrual into the study. Signed informed consents for the performing of BRCA1 and BRCA2 genetic analysis and for enrollment into the study are required. Eligible women will be followed thereafter in order to evaluate the efficacy of exemestane in reducing the incidental rate of breast cancer in unaffected postmenopausal carriers of BRCA1/2 mutations.


Subject(s)
Breast Neoplasms/prevention & control , Anticarcinogenic Agents/therapeutic use , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Female , Genetic Counseling , Humans , Incidence , Mastectomy , Ovariectomy , Risk Factors , Tamoxifen/therapeutic use
7.
Ann Oncol ; 15(5): 726-32, 2004 May.
Article in English | MEDLINE | ID: mdl-15111339

ABSTRACT

BACKGROUND: We describe a multistep model of cancer genetic counselling designed to promote awareness, and disease surveillance and preventive measures for hereditary and familial breast and ovarian cancer. PATIENTS AND METHODS: Step T0 of the model entails information giving; this is followed by pedigree analysis and risk estimation (T1), risk communication and genetic testing (T2), and genetic test result communication (T3). User consent was required to proceed from one step to the next. Surveillance and preventive measures are proposed to at-risk users. Of the 311 subjects who requested cancer genetic counselling, consent data to each counselling step were available for 295: 93 were disease-free, 187 had breast cancer, 12 had ovarian cancer and three had breast plus ovarian cancer. RESULTS: Consent was high at T0 (98.39%), T1 (96.40%) and T2 (99.65%). Consent decreased at the crucial points of counselling: T2 (87.71%) and T3 [genetic test result communication (85.08%), and extension of counselling to and testing of relatives (65.36%)]. CONCLUSIONS: The model fosters the user's knowledge about cancer and favours identification of at-risk subjects. Furthermore, by promoting awareness about genetic testing and surveillance measures, the algorithm enables users to make a fully informed choice of action in case of predisposing or familial cancer risk.


Subject(s)
Breast Neoplasms/genetics , Genetic Counseling , Genetic Predisposition to Disease , Genetic Testing , Informed Consent , Ovarian Neoplasms/genetics , Female , Humans , Patient Education as Topic , Pedigree , Risk Factors
8.
Br J Cancer ; 88(10): 1507-9, 2003 May 19.
Article in English | MEDLINE | ID: mdl-12771913

ABSTRACT

At present, the various mechanisms involved in 5-fluorouracil (5-FU)-correlated cardiotoxicity remain to be elucidated and a universally accepted prophylaxis or treatment for this specific toxicity is not available. Although it may improve time to progression, survival and clinical benefit, a 5-FU-based regimen usually has to be discontinued if a patient experiences cardiotoxicity. Here, we describe our experience with three cases of 5-FU-associated cardiotoxicity. The angina-like pain that appeared approximately 95 h after beginning 5-FU therapy was apparently independent of the drug's administration modality. In the two patients receiving 5-FU 12-h flat continuous infusion from 22.00 to 10.00 h (5-FU 12-h c.i.) in combination with other drugs, the dose of 5-FU was reduced by 10-20% and patients received prophylactic transepidermal nitroglycerin. In the third patient, 5-FU administration modality was changed and prophylactic therapy was not given. By taking these precautions, the patients no longer complained of anginal pain and none of them discontinued chemotherapy.


Subject(s)
Angina Pectoris/chemically induced , Angina Pectoris/prevention & control , Antimetabolites, Antineoplastic/adverse effects , Fluorouracil/adverse effects , Nitroglycerin/therapeutic use , Vasodilator Agents/therapeutic use , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Female , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Humans , Male , Middle Aged , Neoplasms/drug therapy
10.
J Am Coll Cardiol ; 37(7): 1891-900, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11401128

ABSTRACT

OBJECTIVES: The goal of this study was to determine the effects of exercise training (ET) on functional capacity and quality of life (QOL) in patients who received percutaneous transluminal coronary angioplasty (PTCA) or coronary stenting (CS), the effects on the restenosis rate and the outcome. BACKGROUND: It is unknown whether ET induces beneficial effects after coronary angioplasty. METHODS: We studied 118 consecutive patients with coronary artery disease (mean age 57+/-10 years) who underwent PTCA or CS on one (69%) or two (31%) native epicardial coronary arteries. Patients were randomized into two matched groups. Group T (n = 59) was exercised three times a week for six months at 60% of peak VO2. Group C (n = 59) was the control group. RESULTS: Only trained patients had significant improvements in peak VO2 (26%, p < 0.001) and quality of life (26.8%, p = 0.001 vs. C). The angiographic restenosis rate was unaffected by ET (T: 29%; C: 33%, P = NS) and was not significantly different after PTCA or CS. However, residual diameter stenosis was lower in trained patients (-29.7%, p = 0.045). In patients with angiographic restenosis, thallium uptake improved only in group T (19%; p < 0.001). During the follow-up (33+/-7 months) trained patients had a significantly lower event rate than controls (11.9 vs. 32.2%, RR: 0.71, 95% confidence interval [CI]: 0.60 to 0.91, p = 0.008) and a lower rate of hospital readmission (18.6 vs. 46%, RR: 0.69, 95% CI: 0.55 to 0.93, p < 0.001). CONCLUSIONS: Moderate ET improves functional capacity and QOL after PTCA or CS. During the follow-up, trained patients had fewer events and a lower hospital readmission rate than controls, despite an unchanged restenosis rate.


Subject(s)
Angioplasty, Balloon, Coronary/rehabilitation , Coronary Disease/therapy , Exercise , Quality of Life , Stents , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Recurrence
12.
Circulation ; 99(9): 1173-82, 1999 Mar 09.
Article in English | MEDLINE | ID: mdl-10069785

ABSTRACT

BACKGROUND: It is still a matter of debate whether exercise training (ET) is a beneficial treatment in chronic heart failure (CHF). METHODS AND RESULTS: To determine whether long-term moderate ET improves functional capacity and quality of life in patients with CHF and whether these effects translate into a favorable outcome, 110 patients with stable CHF were initially recruited, and 99 (59+/-14 years of age; 88 men and 11 women) were randomized into 2 groups. One group (group T, n=50) underwent ET at 60% of peak &f1;O2, initially 3 times a week for 8 weeks, then twice a week for 1 year. Another group (group NT, n=49) did not exercise. At baseline and at months 2 and 14, all patients underwent a cardiopulmonary exercise test, while 74 patients (37 in group T and 37 in group NT) with ischemic heart disease underwent myocardial scintigraphy. Quality of life was assessed by questionnaire. Ninety-four patients completed the protocol (48 in group T and 46 in group NT). Changes were observed only in patients in group T. Both peak &f1;O2 and thallium activity score improved at 2 months (18% and 24%, respectively; P<0. 001 for both) and did not change further after 1 year. Quality of life also improved and paralleled peak VO2. Exercise training was associated both with lower mortality (n=9 versus n=20 for those with training versus those without; relative risk (RR)=0.37; 95% CI, 0.17 to 0.84; P=0.01) and hospital readmission for heart failure (5 versus 14; RR=0.29; 95% CI, 0.11 to 0.88; P=0.02). Independent predictors of events were ventilatory threshold at baseline (beta-coefficient=0.378) and posttraining thallium activity score (beta-coefficient -0.165). CONCLUSIONS: Long-term moderate ET determines a sustained improvement in functional capacity and quality of life in patients with CHF. This benefit seems to translate into a favorable outcome.


Subject(s)
Exercise Therapy/methods , Heart Failure/therapy , Quality of Life , Aged , Echocardiography , Exercise Therapy/adverse effects , Female , Heart Failure/diagnostic imaging , Heart Failure/metabolism , Heart Failure/physiopathology , Hemodynamics , Humans , Male , Middle Aged , Multivariate Analysis , Myocardium/metabolism , Patient Readmission , Prospective Studies , Radionuclide Imaging , Survival Analysis , Thallium Radioisotopes , Treatment Outcome
13.
Circulation ; 97(6): 553-61, 1998 Feb 17.
Article in English | MEDLINE | ID: mdl-9494025

ABSTRACT

BACKGROUND: There is evidence that exercise training can induce myocardial and coronary adaptations in both animals and humans. However, the significance of these potentially important changes remains to be determined in patients with ischemic heart disease and left ventricular (LV) systolic dysfunction. METHODS AND RESULTS: To investigate whether exercise training can improve thallium uptake and the contractile response to low-dose dobutamine of dysfunctional myocardium, 46 patients (42 men, 4 women; mean age, 57+/-9 years) with chronic coronary artery disease and impaired LV systolic function (ejection fraction < 40%) were randomly assigned to two groups. The exercise group (n = 26) underwent exercise training at 60% of peak oxygen uptake for 8 weeks. The control group (n = 20) was not exercised. At baseline and after 8 weeks all patients underwent an exercise test with gas exchange analysis and stress echocardiography using low-dose dobutamine (5 to 10 microg/kg per minute) followed by thallium myocardial scintigraphy. Coronary angiography was performed in 23 patients at baseline and after 8 weeks. After 8 weeks, peak oxygen uptake increased significantly only in trained patients (24%). Significant improvements in the contractile response to dobutamine and thallium activity were observed in trained patients (28% and 31%, respectively; trained versus control: P<.001 for both). In a subgroup of trained patients, both improvements were correlated with an increase in the coronary collateral score (P<.005 and P<.001, respectively). CONCLUSIONS: Moderate exercise training improves both thallium activity and the contractile response of dysfunctional myocardium to low doses of dobutamine in patients with ischemic cardiomyopathy. The implication of this study is that even a short-term exercise training may improve quality of life by improvement of LV systolic function during mild-to-moderate physical activity in patients with ischemic cardiomyopathy.


Subject(s)
Exercise Therapy , Myocardial Contraction , Myocardial Ischemia/physiopathology , Myocardial Ischemia/therapy , Adaptation, Physiological , Adrenergic beta-Agonists , Aged , Collateral Circulation , Dobutamine , Echocardiography , Female , Humans , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Radionuclide Imaging , Statistics, Nonparametric , Thallium Radioisotopes , Ventricular Function, Left
14.
Am Heart J ; 132(1 Pt 1): 61-70, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8701877

ABSTRACT

The aim of our study was to determine whether exercise training can augment left ventricular diastolic filling at rest and during exercise in patients with ischemic cardiomyopathy and whether any correlation exists between changes in diastolic filling and changes in exercise tolerance. Forty-three consecutive patients (mean age, 54 +/- 8 years) with ischemic cardiomyopathy and severe left ventricular systolic dysfunction (election fraction <30%) were studied. Group T (29 patients) was exercised on a cycle ergometer 3 times a week for 8 weeks at 60% of peak oxygen uptake. Group C (14 patients) was not exercised. All patients underwent an exercise test and a radionuclide ventriculography at baseline and after 8 weeks. At the end, no changes were found in group C. In group T, exercise training increased peak oxygen uptake (1 5%; p < 0.0001), work rate (1 5%; p < 0.005), peak early filling rate (10%; p < 0.02), and peak filling rate (1 1%; p < 0.03). At submaximal exercise, peak filling rate increased at all matched heart rates. The increase in peak filling rate was correlated with the increase in cardiac index (r= 0.72; p < 0.0001) at peak exercise. The independent predictors of the increase in peak oxygen uptake were changes in work capacity and peak early filling rate. The data demonstrate that exercise training can improve the exercise capacity of patients with ischemic cardiomyopathy and severe systolic-dysfunction. The increase in early diastolic filling at rest and during exercise may contribute to the improvement in peak oxygen uptake.


Subject(s)
Cardiac Output , Exercise Therapy , Exercise , Myocardial Ischemia/physiopathology , Rest , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left , Diastole , Exercise Test , Exercise Tolerance , Female , Forecasting , Heart Rate , Humans , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/rehabilitation , Oxygen Consumption , Prospective Studies , Radionuclide Ventriculography , Stroke Volume , Systole , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/rehabilitation
15.
Circulation ; 91(11): 2775-84, 1995 Jun 01.
Article in English | MEDLINE | ID: mdl-7758184

ABSTRACT

BACKGROUND: Patients with dilated cardiomyopathy (DCM) often have left ventricular (LV) diastolic dysfunction that can precede the development of systolic dysfunction. Recent reports showed that exercise training (ET) improves the exercise capacity of these patients. Although this improvement is primarily due to peripheral adaptations, the contribution of LV diastolic filling has not been well defined. The purpose of this study was to determine whether ET can induce changes in LV diastolic filling that can account for an increase in exercise capacity and whether these changes can influence prognosis. METHODS AND RESULTS: We prospectively studied 55 consecutive patients (mean age, 55 +/- 7 years) with DCM. Patients were randomized into a training group (36 patients) or a control untrained group (19 patients) and matched for clinical and functional characteristics. All patients underwent a pulsed Doppler echocardiographic study, a radionuclide angiographic study, and a cardiopulmonary exercise test before and after a 2-month ET program. On the basis of the Doppler LV diastolic filling pattern at the beginning of the study, patients were prospectively divided into three subgroups: A (restrictive pattern), B ("normal" pattern), and C (abnormal relaxation pattern). In the trained group, peak VO2 (+12%; P < .0001), peak workload (+8.5%; P < .005), and lactic acidosis threshold (+12%; P < .0001) were significantly increased after training without changes in LV ejection fraction. However, only subgroup C demonstrated significant improvement in peak VO2 (+15%; P < .005). No changes were observed in the untrained group. In the trained subgroups a significant increase in rapid filling fraction (RFF), peak filling rate (PFR), peak early filling velocity (E), and E/A ratio was noted. A significant decrease in atrial filling fraction (AFF), peak atrial filling velocity (A), deceleration time of early filling velocity (EDT), and isovolumic relaxation time (IVRT) was observed only in subgroup C. No changes were found in untrained subgroups. A good correlation was found between Doppler and radionuclide LV diastolic filling parameters before and after training (P < .0001). Multiple stepwise regression analysis demonstrated that pretraining E/A ratio (P < .0001) and peak heart rate (P < .0002) were positive predictors of pretraining peak VO2. Posttraining increase in exercise tolerance (P < .0001) and increase in E/A ratio (P < .0001) were the strongest predictors of an increase in peak VO2. The independent predictors of cardiac events were a greater RFF and a shorter IVRT and EDT. Stepwise logistic regression showed that Doppler LV diastolic filling patterns are independent predictors of overall cardiac events (P = .02), and restrictive pattern has a worse prognosis compared with B (P = .04) and C (P = .007). However, ET did not reach statistical significance (P = .54) as a predictor of cardiac events. CONCLUSIONS: These data demonstrate that ET induces significant improvement in exercise capacity only in patients with DCM and a pattern of abnormal LV relaxation. The improvement in peak VO2 is significantly correlated with an increase in peak early filling rate and peak filling rate as well as a decrease in atrial filling rate. Doppler echocardiography may be a valuable tool in the prognostic assessment of patients with DCM who will benefit from exercise training.


Subject(s)
Cardiomyopathy, Dilated/rehabilitation , Exercise Therapy , Ventricular Function, Left/physiology , Blood Flow Velocity/physiology , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/physiopathology , Coronary Circulation/physiology , Diastole/physiology , Disease-Free Survival , Echocardiography, Doppler, Pulsed , Exercise Test , Exercise Tolerance/physiology , Female , Gated Blood-Pool Imaging , Humans , Male , Middle Aged , Mitral Valve/diagnostic imaging , Multivariate Analysis , Prognosis , Proportional Hazards Models , Prospective Studies , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/physiopathology
17.
Radiol Med ; 66(9): 591-5, 1980 Sep.
Article in Italian | MEDLINE | ID: mdl-7232787

ABSTRACT

In 131 verified cases with known primitive tumor, the diagnostic accuracy of the echotomography resulted in 84% (sensitivity 89%; specificity 76%). Technical insufficiency of the echotomography did not define the diagnosis in 8% of the patients. The evidence of solid lesions in both lobes of the liver and the involvement of the inferior vena cava are the criteria for inoperability and selection for angiographic test. The diagnostic value of the echotomography was low in cases where the primitive tumour was not identified because of the non specificity of the echo-structure of the solid intrahepatic lesions. Angiography is essential when a liver resection is planed.


Subject(s)
Angiography/standards , Echocardiography/standards , Liver Neoplasms/secondary , Tomography/standards , Humans , Liver Neoplasms/diagnostic imaging
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