Light scattering from cervical cells throughout neoplastic progression: influence of nuclear morphology, DNA content, and chromatin texture.

A number of noninvasive fiber optic optical technologies are under development for real-time diagnosis of neoplasia. We investigate how the light scattering properties of cervical cells are affected by changes in nuclear morphology, DNA content, and chromatin texture, which occur during neoplastic progression. We used a Cyto-Savant computer-assisted image analysis system to acquire quantitative nuclear features measurements from 122 Feulgen-thionin-stained histopathologic sections of cervical tissue.

Cytometric features of cell nuclei of adenocarcinoma in situ and invasive adenocarcinoma of the cervix.

Objective: The goal of this study was to characterize adenocarcinoma in situ (ACIS) and invasive adenocarcinoma (AdCa) of the cervix by using image histometric measurements of nuclear morphometric features.

Study Design: Archival pathology slides and tissue blocks from 37 patients with ACIS, 18 with invasive AdCa, and 13 with normal cervical epithelial and glandular histology were reviewed by two pathologists. The controls were matched for age and menstrual status and as closely as possible for the age of the slides; this limited the number of normal cases available.

Optimal excitation wavelengths for discrimination of cervical neoplasia.

Fluorescence spectroscopy has shown promise for the in vivo, real-time detection of cervical neoplasia. However, selection of excitation wavelength has in the past been based on in vitro studies and the availability of light sources. The goal of this study was to determine optimal excitation wavelengths for in vivo detection of cervical neoplasia.

Innovative molecular and imaging approaches for the detection of lung cancer and its precursor lesions.

Current approaches for the therapy of lung cancer, the majority of which being advanced cancers, have failed to impact on long term survival. The key to improvement lies in the combination of early diagnosis and the introduction of novel targeted therapies. In this article we review some of the innovative approaches, both imaging and molecular, that are currently under investigation for early detection.

Increase of sensitivity of sputum cytology using high-resolution image cytometry: field study results.

Lung cancer remains the leading cause of cancer deaths in the developed world. There is no widely accepted method to screen for this cancer. The most commonly used method remains conventional sputum cytology, but this method is hampered by low sensitivity.

A randomized phase IIb trial of anethole dithiolethione in smokers with bronchial dysplasia.

Background: Results from preclinical studies have suggested that the organosulfur compound anethole dithiolethione (ADT) may be an effective chemopreventive agent for lung cancer. We conducted a phase IIb study to determine the effects of ADT in smokers with bronchial dysplasia.

Methods: One hundred twelve current and former smokers with a smoking history of at least 30 pack-years and at least one site of bronchial dysplasia identified by an autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive placebo or ADT at 25 mg orally thrice daily for 6 months.

Variation of fluorescence spectroscopy during the menstrual cycle.

Cervical autofluorescence has been demonstrated to have potential for real-time diagnosis. Inter-patient and intra-patient variations in fluorescence intensity have been measured. Inter-patient measurements may vary by a factor of ten, while intra-patient measurements may vary by a factor of two.

Monitoring photoproduct formation and photobleaching by fluorescence spectroscopy has the potential to improve PDT dosimetry with a verteporfin-like photosensitizer.

In current clinical practice, photodynamic therapy (PDT) is carried out with prescribed drug doses and light doses as well as fixed drug-light intervals and illumination fluence rates. This approach can result in undesirable treatment outcomes of either overtreatment or undertreatment because of biological variations between different lesions and patients. In this study, we explore the possibility of improving PDT dosimetry by monitoring drug photobleaching and photoproduct formation.

Nuclear texture features for classifying benign vs. dysplastic or malignant squamous epithelium of the larynx.

Objective: To search for nuclear features and feature combinations able to assess malignancy and premalignant changes on tissue sections of laryngeal squamous epithelium.

Study Design: A total of 139 lesions of benign changes (BC) (n = 44), epithelial dysplasias (ED) (n = 50) and invasive laryngeal cancer (LC) (n = 45) were retrieved from archival pathology specimens. The goal of this study was to identify the best features or feature combinations that discriminate BC from LC and also reflect the degree of ED.

Therapeutic value of eptifibatide at community hospitals transferring patients to tertiary referral centers early after admission for acute coronary syndromes. PURSUIT Investigators.

Objectives: We aimed to evaluate the benefits of the glycoprotein (GP) IIb/IIIa antagonist, eptifibatide, after patients with acute coronary syndromes (ACS) were admitted to hospitals that approach revascularization for ACS through early transfer to tertiary referral centers.

Background: Across a variety of hospital settings, GP IIb/IIIa inhibition, after patients were admitted to the hospital for non-ST segment elevation ACS, is associated with a reduction in death or myocardial infarction (MI) before and during a percutaneous coronary intervention.

Methods: The outcomes of 429 patients from 153 sites in the Platelet glycoprotein IIb/IIIa in unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, who were transferred during study drug infusion ("transfer patients"), were compared with those of 1,987 patients who either remained in the hospital at those sites or were transferred after study drug termination ("nontransfer patients").

Specific changes of chromatin structure in nuclei of normal epithelium adjacent to laryngeal squamous cell carcinoma. A preliminary study of 82 cases.

The aim of this study was to confirm the existence of specific nuclear texture feature alterations of histologically normal epithelial borders nearby invasive laryngeal cancer (NC). Paraffin sections of NC and of chronic inflammations unrelated to cancer (CI) were analysed for nuclear texture and for integrated optical density (IOD-index) and were compared to normal epithelium of patients without evidence of cancer (NE). Several discriminant functions based on nuclear texture features were trained to separate different subgroups.

Detection and localization of early lung cancer by fluorescence bronchoscopy.

Background: Curative therapy is available for patients with Stage 0 lung carcinoma, with a >90% 5-year survival rate. Promising chemopreventive agents also are under investigation currently to reduce the risk of lung carcinoma in high risk populations. However, preinvasive bronchial lesions (moderate to severe dysplasia and carcinoma in situ) are very small and thin.

The complete DNA sequence of myxoma virus.

Myxomatosis in European rabbits is a severely debilitating disease characterized by profound systemic cellular immunosuppression and a high rate of mortality. The causative agent, myxoma virus, is a member of the poxvirus family and prototype of the Leporipoxvirus genus. As a major step toward defining the genetic strategies by which the virus circumvents host antiviral responses, the genomic DNA sequence of myxoma virus, strain Lausanne, was determined.

Nuclear morphometry as an intermediate endpoint biomarker in chemoprevention of cervical carcinoma using alpha-difluoromethylornithine.

The use of nuclear morphometry as an intermediate endpoint biomarker is described in a Phase I, dose-seeking trial of chemoprevention of cervical cancer, using the agent alpha-difluoromethylornithine (DFMO). Thirty patients with grade III cervical intraepithelial neoplasia (CIN III) were enrolled, and these received daily doses of DFMO at 0.06-1.

New method for detection of heart allograft rejection: validation of sensitivity and reliability in a rat heterotopic allograft model.

Background: Patients with inflammatory heart muscle diseases would benefit from a safe, convenient, rapidly performed diagnostic technique with real-time results not involving tissue removal. We have performed a detailed evaluation of detection of heart allograft rejection by autofluorescence in a heterotopic abdominal rat heart allograft model ex vivo.

Methods And Results: Recipient rats with allograft (Lewis to Fisher 344; n=71) and isograft (Lewis to Lewis; n=33) hearts, treated with cyclosporine or untreated, were killed at days 2, 4, 7, 14, 21, 28, and 56 after transplant.

Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.

Background: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates.

Methods And Results: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.

Sex-related differences in bronchial epithelial changes associated with tobacco smoking.

Background: Lung cancer is the most common cause of cancer death in North American women. Because smoking-related changes in the bronchial epithelium and in lung function have not been studied in detail in women, we used fluorescence bronchoscopy-directed biopsy to determine the prevalence of high-grade preinvasive lesions in former and current smokers of both sexes.

Methods: Spirometry, white-light bronchoscopy, and fluorescence bronchoscopy were performed in 189 women and 212 men older than 40 years of age who had smoked 20 pack-years or more (pack-years = number of packs of cigarettes smoked per day x number of years of smoking).

The dynamics of laser-induced changes in human skin autofluorescence--experimental measurements and theoretical modeling.

To study the temporal dynamics of human skin autofluorescence photobleaching, we measured the autofluorescence spectral changes of skin in vivo during continuous exposure to 442 nm (He-Cd) laser light. Integral intensities were calculated for various spectral wavelength bands and plotted as a function of time. Mathematical analysis of the time function revealed a double-exponential photobleaching process: I(t) = a exp (-t/tau 1) + b exp(-t/tau 2) + c, in which tau 1 and tau 2 differed by an order of magnitude.

Malignancy associated changes in bronchial epithelial cells and clinical application as a biomarker.

A total of 74 bronchial brushing specimens, 24 from patients with advanced stage cancer, eight from patients with CIS, 31 from patients with atypical metaplasia and 11 from normal subjects were examined for the existence of malignancy associated changes (MAC). Conventional fiberoptic bronchoscopy and fluorescence endoscopy was carried out on every case. Each case was classified according to the highest grade of abnormality diagnosed by bronchial biopsy of the suspect areas.

Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO-IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-IIb) Investigators.

Objectives: We sought to show that hirudin might interact differently with streptokinase (SK) and tissue-type plasminogen activator (t-PA), which could reduce the incidence of death or reinfarction at 30 days.

Background: In a large-scale trial of patients with acute coronary syndromes, hirudin provided modest benefit compared with heparin. However, the interaction with thrombolytic agents was not specifically assessed.

DNA-cytometry of progressive and regressive cervical intraepithelial neoplasia.

A retrospective analysis was performed on archival cervical smears from a group of 56 women with cervical intraepithelial neoplasia (CIN), who had received follow-up by cytology only. Automated image cytometry of Feulgen-stained DNA was used to determine the differences between progressive and regressive lesions. The first group of 30 smears was from women who had developed cancer after initial smears with dysplastic changes (progressive group).

The use of an automated image cytometer for screening and quantitative assessment of cervical lesions in the British Columbia Cervical Smear Screening Programme.

The development of an automated device to screen cervical cytology slides for the detection of pre-invasive lesions of the cervix has been the goal of many individuals for over 30 years. The increasing sophistication of the technology of automation and increasingly powerful computer technology have enabled a number of these systems to reach the stage at which they have become a practical reality. The Department of Cancer Imaging at the British Columbia Cancer Agency has developed such a device over the past few years.

Sputum screening by quantitative microscopy: a reexamination of a portion of the National Cancer Institute Cooperative Early Lung Cancer Study.

Objective: To investigate the hypothesis that image cytometry of sputum specimens can detect squamous carcinoma without requiring visually abnormal cells.

Design: The sensitivity and specificity of image cytometry were evaluated in a case-control study.

Material And Methods: Seventy-three sputum slides from the Mayo portion of the National Cancer Institute Cooperative Early Lung Cancer Study were restained by a modified Feulgen method.

Reconstruction of in vivo skin autofluorescence spectrum from microscopic properties by Monte Carlo simulation.

The in vivo skin autofluorescence spectrum was reconstructed by Monte Carlo simulation using microscopic fluorophore distributions and intrinsic fluorescence spectra measured from excised skin tissue sections as well as employing published skin tissue optical parameters. The theoretical modeling took into account the light-tissue interactions of scattering, absorption, and regeneration of fluorescence photons. The modification of the intrinsic spectra by tissue optical properties to generate the in vivo spectrum observed at the tissue surface can be represented by a fluorescence detection efficiency function (eta) which equals the integral of the product of the excitation light distribution inside the tissue and the fluorescence escape efficiency.