Positron emission tomography imaging in nonmalignant thoracic disorders

The role of the fluorodeoxyglucose (FDG) technique positron emission tomography (PET) is well established in the management of patients with lung cancer. Increasingly, it is becoming evident that FDG-PET can be effectively employed to diagnose a variety of benign pulmonary disorders. Knowledge of such applications further expands the domain of this powerful modality and further improves the ability to differentiate benign from malignant diseases of the chest. We describe pertinent technical factors that substantially contribute to optimal imaging of the thoracic structures. Particularly, the complementary role of attenuation correction (AC) to that of non-AC images is emphasized. We further outline the need for and the state of the art for co-registration of PET and anatomic images for diagnostic and therapeutic purposes. We then review patterns of physiologic uptake of FDG in thoracic structures, including the lung, the heart, the aorta and large arteries, esophagus, thymus, trachea, thoracic muscles, bone marrow, and joints and alterations following radiation therapy to the thorax. A great deal of information is provided with regard to differentiating benign from malignant nodules and in particular, we emphasize the role of dual time point imaging and partial volume correction for accurate assessment of such lesions. Following a brief review of the diagnostic issues related to the assessment of mediastinal adenopathies, the role of FDG-PET imaging in environment-induced lung diseases, including pneumoconiosis, smoking, and asthma are described. A large body of information is provided about the role of this technology in the management of patients with suspected infection and inflammation of the lungs such as acquired immunodeficiency syndrome, fever of unknown origin, sarcoidosis, chronic granulomatous disease and monitoring the disease process and response to therapy. Finally, the value of FDG-PET in differentiating benign from malignant diseases of the pleura including asbestosis-related disorders is described at the conclusion of this comprehensive review.     

The effect of moving textures on the responses of cells in the cat's dorsal lateral geniculate nucleus

Neurons in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized cat were activated with test stimuli (flashing spots, counterphased gratings and moving bars) in the presence of a moving background texture. Moving texture alone produced mild excitation, as a result of stimulation of the receptive field centre. Fast moving coarse textures were more effective than fine slow moving textures. The predominant effect of texture motion, however, was to reduce the response to all test stimuli displayed in the receptive field centre. The effects were similar for X- and Y-like cells. In the case of flashed spots, the sustained response was more strongly suppressed than the transient response. The direction of motion of the texture and differences in the relative motion of bar and texture had no influence on the degree of suppression. These observations are similar to effects seen on cat retinal ganglion cells, and are probably a form of gain control. Such suppressive effects are transmitted to the cortex and are likely to be evoked by large gratings, textures and by natural stimuli, all of which activate extensive regions of the receptive field surround.     

Combination chemotherapy without cisplatin in the treatment of advanced non-small cell lung cancer

Cisplatin-based combinations are standard regimens in the treatment of advanced non-small cell lung cancer. Survival improvement has been achieved using this therapy. However, the high toxicity induced by cisplatin-based doublets urges the research of alternate treatments. Newest cytotoxic compounds yield a better efficacy-toxicity ratio. Platinum-free doublet regimens based on new drugs are expected to offer the patient an improved survival without decreasing his quality of life. Treatment-allocated time and period with high grade toxicity could be considered as wasted from the patient point of view. QUALY methods based on time without symptoms and toxicity allow the accurate evaluation of this end-point. This brief state-of-the-art deals with methodological statements highlighted by the first publications of randomized studies comparing non-platinum-based doublets with either single-drug chemotherapy or standard cisplatin-based doublets.     

Scarff-Bloom-Richardson (SBR) grading: a pleiotropic marker of chemosensitivity in invasive ductal breast carcinomas treated by neoadjuvant chemotherapy

The Scarff-Bloom-Richardson (SBR) grade, an important prognostic factor in breast cancer, was also associated with cell proliferation, a consistent indicator of response to chemotherapy. The determination of an association between SBR grade and responsiveness would be clinically useful. We explored the influence of SBR grade on response to neoadjuvant chemotherapy in patients with invasive ductal breast carcinoma. The present study centered on 431 patients registered onto one of four prospective phase II trials. SBR grading was performed according to the Elston method on needle core biopsies prospectively collected prior to treatment from 290 patients and on residual tumour at surgery from 171 patients. The post-operative grades were then compared with those obtained at diagnosis. Univariate and multivariate analysis were used to evaluate the significance of SBR grade on response to neoadjuvant chemotherapy. Both statistical analysis revealed that SBR grade III tumours responded better to neoadjuvant treatment than SBR grade I (p<10(-6)). None of the other patient and tumour characteristics tested correlated with response. Moreover, tumour responsiveness was significantly related to changes of the SBR grade (p=7 x 10(-3)). As a conclusion, we showed that SBR grade is a strong predictive factor of response to induction chemotherapy in breast cancer, independently of the type of regimen used. The association between evolution of the histological grade following chemotherapy and response to treatment may prove valuable for clinicians as they make their decision regarding patient therapy.     

Chemotherapy for metastatic breast cancer-report of a European expert panel

The anthracyclines doxorubicin and epirubicin, and the taxanes paclitaxel and docetaxel, are effective chemotherapeutic agents for the first-line and second-line treatment of metastatic breast cancer, and their clinical use is widespread. However, for women whose disease has progressed despite receiving these drugs, treatment options are limited. These women often have a good performance status, and may survive for many months or even years, so they should be given the opportunity to benefit from further chemotherapy. The goals of chemotherapy in these patients are to obtain maximum control of symptoms, prevent serious complications, and increase survival without diminishing quality of life. Several agents are used for this purpose, including fluorouracil, docetaxel (in patients who have already received paclitaxel), vinorelbine, and mitomycin c, but because data from controlled trials are limited, a standard regimen has not yet been established. Moreover, these agents may be inconvenient to administer and can be associated with adverse events requiring hospitalisation. Therefore, there is a clear need for additional therapeutic options for patients with metastatic breast cancer. Ideally, agents should have a convenient method of administration, eg, oral, and should be suitable for home-based rather than hospital-based therapy. Treatment should control disease in at least 20-30% of patients with an acceptable side-effect profile. Novel oral therapies have now been developed and are being used increasingly in patients whose disease has progressed following taxane therapy.     

2000 Standards,Options and Recommendations for prognostic value of oncogenes and tumor suppressor genes in non small cell lung cancer

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for non small cell lung cancer patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers. RESULTS: This article presents the chapter "Prognosis significance of oncogenes and tumor suppressor genes" from the full report "Standards, Options and Recommendation for non small cell lung cancer" validated in August 2000. The main recommendations are: 1) No clear clinical prognostic value of oncogenes and tumor suppressor genes (p53, bcl-2, Ki-ras, c-erbB-2, Rb, p16) in non small cell lung cancer, can be established from the available evidences (standard, level of evidence C). 2) Prospective multicenter studies should be performed to assess prognostic significance of oncogenes and tumor suppressor genes in non small cell lung cancer.     

Sleep complaints and visual impairment among older Americans: a community-based study

BACKGROUND: This report describes the associations between sleep complaints and reported visual impairment in an urban community-residing older adult sample. METHODS: A total of 1118 volunteers from a biracial cohort participated in the study (mean age = 74 +/- 6; mean body mass index = 28 +/- 10). Volunteers were recruited using a stratified, cluster sampling technique. In a standard order, several questionnaires were administered, soliciting information on socioeconomic status, physical health, social support, and emotional experience. The physical health questionnaire included questions on whether or not the volunteer experienced sleep disorder, visual impairment, heart disease, respiratory disease, arthritis, and hypertension. In this report, we present data on the prevalence of reported sleep problems and visual impairment among older adults. RESULTS: Of the total sample, 9% used sleep medicine, 25% reported difficulty falling asleep, 52% indicated experiencing difficulty maintaining sleep, 28% reported waking up early in the morning, and 12% reported daytime sleep longer than 2 hours. Chi-square results showed greater sleep complaints for volunteers with visual impairment. Consistent with these results, analysis of variance revealed that visually impaired volunteers had a higher index rate of sleep disturbance (F((1, 1110)) = 35.32, p <.0001). CONCLUSIONS: These data provide evidence that older adults reporting visual impairment are also likely to report sleep complaints. This verifies laboratory findings of an association of ophthalmic diseases with sleep-wake problems and with circadian rhythm abnormalities.     

Cutis marmorata telangiectatica congenita: report of two persistent cases

Cutis marmorata telangiectatica congenita (CMTC) is defined as a localized or generalized reticulated, blue-violet vascular network in skin that is present at birth. The evolution is characterized by rapid improvement within 2 years. Rarely the lesions do not improve very much with age. Few reports include long-term follow-up of CMTC. We report two patients with persistent CMTC, including one with nervous breakdown and failure of laser treatment. The cause and incidence of persistent CMTC is unknown. Parents can be counseled that over time the lesions of CMTC may or not improve. There seems to be no predictive clinical sign. CMTC is usually a benign condition and therapy is rarely discussed. Treatment of persistent CMTC seems difficult and the effectiveness of laser therapy needs to be evaluated.     

Coherent infrared emission from myoglobin crystals: an electric field measurement

We introduce coherent infrared emission interferometry as a chi(2) vibrational spectroscopy technique and apply it to studying the initial dynamics upon photoactivation of myoglobin (Mb). By impulsive excitation (using 11-fs pulses) of a Mb crystal, vibrations that couple to the optical excitation are set in motion coherently. Because of the order in the crystal lattice the coherent oscillations of the different proteins in the crystal that are associated with charge motions give rise to a macroscopic burst of directional multi-teraHertz radiation. This radiation can be detected in a phase-sensitive way by heterodyning with a broad-band reference field. In this way both amplitude and phase of the different vibrations can be obtained. We detected radiation in the 1,000-1,500 cm(-1) frequency region, which contains modes sensitive to the structure of the heme macrocycle, as well as peripheral protein modes. Both in carbonmonoxy-Mb and aquomet-Mb we observed emission from six modes, which were assigned to heme vibrations. The phase factors of the modes contributing to the protein electric field show a remarkable consistency, taking on values that indicate that the dipoles are created "emitting" at t = 0, as one would expect for impulsively activated modes. The few deviations from this behavior in Mb-CO we propose are the result of these modes being sensitive to the photodissociation process and severely disrupted by it.     

Brain function in the vegetative state

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.