Micro-computed tomography of the lungs and pulmonary-vascular system

Three-dimensional imaging of the intact lung and its vasculature is essential if the hierarchical and volumetric aspects of its structures and functions are to be quantitated. Although this is possible with clinical multislice helical CT scanners, the spatial resolution does not scale down adequately for small rodents for which cubic voxel dimensions of 50-100 microm are required. Micro-computed tomography (micro-CT) provides the necessary spatial resolution of 3D images of the intact thoracic contents. Micro-CT can provide higher resolution so that basic micro-architectural structures, such as alveoli, can be individually visualized and quantitated. Dynamic events, such as the respiratory and cardiac cycles, can be imaged at multiple time points throughout a representative cycle by coordinating the scan sequence (i.e., gating) to the cycle phase of a sequence of cycles. Fusion of the micro-CT image data with other image data, such as micro-SPECT or histology, can enhance the information content beyond the mainly structural information provided by micro-CT. Conventional attenuation-based X-ray imaging can involve significant X-ray exposures at high spatial resolutions, and this could affect the phenotype (e.g., via interstitial fibrosis) and genotype (e.g., via mutation), so its use in longitudinal studies using micro-CT may be limited in some cases. However, because of recent developments in which the phase shift or refraction of X-rays rather than attenuation is used, the X-ray exposure may be significantly reduced.     

Genes mediating environment interactions in type 1 diabetes

The relative risk of type 1 (autoimmune) diabetes mellitus for a sibling of an affected patient is fifteen times that of the general population, indicating a strong genetic contribution to the disease. Yet, the incidence of diabetes in most Western communities has doubled every fifteen years since the Second World War - a rate of increase that can only possibly be explained by a major etiological effect of environment. Here, the authors provide a selective review of risk factors identified to date. Recent reports of linkage of type 1 diabetes to genes encoding pathogen pattern recognition molecules, such as toll-like receptors, are discussed, providing a testable hypothesis regarding a mechanism by which genetic and environmental influences on disease progress are integrated.     

A psychophysical study of visual extinction: ipsilesional distractor interference with contralesional orientation thresholds in visual hemineglect patients

Visual extinction was investigated in left (n=15) and right (n=25) brain-damaged patients with or without visual neglect, and in normal control subjects (n=14), using a psychophysical paradigm. Orientation discrimination thresholds were determined for both left and right hemifield gratings presented either in isolation or simultaneously with a contralateral distractor grating. To minimize the influence of possible sensory-perceptual deficits, the luminances of both target and distractor gratings were chosen to be 20 times the luminances necessary to discriminate between horizontal and vertical grating orientations. The location of the target grating was always cued, making the distractor grating task irrelevant. Even after equalizing the visibility of left and right hemifield stimuli, neglect patients still displayed an increased interference effect from an ipsilesional distractor (and no interference from a contralesional distractor). Left or right brain-damaged controls did not show this asymmetric interference of irrelevant distractors, even the patients who demonstrated extinction on standard extinction testing. This suggests that visual extinction is a critical component of the visual neglect syndrome and that it involves an attentional deficit.     

Electrophysiological signs of permanent axonal loss in a follow-up study of patients with Guillain-Barré syndrome

The neurophysiological mechanisms for persisting impairment of motor function after Guillain-Barre syndrome (GBS) were assessed in 37 unselected patients 1-13 years after diagnosis. For evaluation of reinnervation and axonal loss, macroelectromyography (macro-EMG) including measurement of fiber density (FD) was performed. Data from neuropathy symptom score, neuropathy disability score, nerve conduction studies, and quantitative sensory examination were ranked and summed to a neuropathy rank sum score (NRSS). The isokinetic muscle strength at the ankle was measured. Signs of axonal loss with increase of either macro motor unit potential (macro-MUP) amplitude or FD occurred in 76% of patients. The macro-MUP amplitude correlated with muscle strength and with NRSS. Patients with evidence of residual neuropathy had increased macro-MUP amplitude and FD as well as decreased muscle strength compared to patients without evidence of residual neuropathy. We conclude that axonal loss takes place in a substantial number of GBS patients and is associated with permanent muscle weakness caused by insufficient reinnervation. Possible patterns of pathology are discussed in relation to the macro-EMG findings.     

Intravenous immunoglobulin ameliorates experimental autoimmune encephalomyelitis and reduces neuropathological abnormalities when administered prophylactically

BACKGROUND AND METHODS: Immunomodulation with intravenous immunoglobulin (IVIG) represents a way of interfering with the disease process in multiple sclerosis (MS). In this study, the effects of IVIG on neurological symptoms and central nervous system (CNS) pathology were evaluated in experimental autoimmune encephalomyelitis (EAE), an MS animal model. EAE was induced in susceptible Dark Agouti rats by active immunization with a spinal cord homogenate, and infusions of 1 g/kg IVIG were given prophylactically or therapeutically.RESULTS: The administration of IVIG at the time of immunization significantly suppressed the development of neurological symptoms compared with infusions of placebo (mean EAE score 0.6+/-0.3 versus 2.3+/-0.4). Moreover, the prophylactic IVIG administration resulted in a significant inhibition of the inflammatory response in CNS tissue (inflammation score 1.1+/-0.2 versus 1.8+/-0.2 after placebo). No beneficial effects were obtained by therapeutic IVIG infusions as the EAE disease course and the degree of inflammation and demyelination in the CNS were not different from animals receiving treatment with placebo.CONCLUSIONS: The present study indicates that IVIG reduces the symptoms of EAE by suppression of the CNS inflammation that characterizes CNS pathology in these animals. Taking into account data from clinical trials of IVIG in MS, the results further suggest that IVIG acts primarily during the induction phase of the immune response thus preventing the development of relapses in MS.     

Subjective Health Complaints and Modern Health Worries in Patients with Subjective Food Hypersensitivity

Perceived food hypersensitivity is much more common than food allergy as medically verified. Unexplained symptoms and wrong attribution are typical in subjective health complaints. We hypothesize that subjective health complaints and worries are abnormally prevalent among patients with subjective food hypersensitivity. Forty-six patients with subjective food hypersensitivity and two control groups, one formed by 50 health care workers and one by 70 sex- and age-matched volunteers from the general population, were included in our study. All filled in two questionnaires: Subjective Health Complaints Inventory and Modern Health Worries Scale. None of the patients had IgE-mediated food allergy. The patients scored significantly higher than the controls on sum scores for four domains of subjective health complaints, including gastrointestinal complaints (P < 0.001), musculoskeletal complaints (P < 0.01), “pseudoneurology” (P < 0.001), and allergy (P < 0.001). Sum scores on modern health worries did not differ significantly between groups. The results support our hypothesis of an association between subjective food hypersensitivity and subjective health complaints, corroborating the view that, in the absence of food allergy, the conditions are sharing pathogenetic mechanisms.     

Hyperbaric Oxygen and Radiotherapy

BACKGROUND: Hyperbaric oxygen (HBO) therapy is the inhalation of 100% oxygen at a pressure of at least 1.5 atmospheres absolute (150 kPa). It uses oxygen as a drug by dissolving it in the plasma and delivering it to the tissues independent of hemoglobin. For a variety of organ systems, HBO is known to promote new vessel growth into areas with reduced oxygen tension due to poor vascularity, and therewith promotes wound healing and recovery of radiation-injured tissue. Furthermore, tumors may be sensitized to irradiation by raising intratumoral oxygen tensions. METHOD: A network of hyperbaric facilities exists in Europe, and a number of clinical studies are ongoing. The intergovernmental framework COST B14 action "Hyperbaric Oxygen Therapy" started in 1999. The main goal of the Working Group Oncology is preparation and actual implementation of prospective study protocols in the field of HBO and radiation oncology in Europe. RESULTS: In this paper a short overview on HBO is given and the following randomized clinical studies are presented: a) reirradiation of recurrent squamous cell carcinoma of the head and neck after HBO sensitization; b) role of HBO in enhancing radiosensitivity on glioblastoma multiforme; c) osseointegration in irradiated patients; adjunctive HBO to prevent implant failures; d) the role of HBO in the treatment of late irradiation sequelae in the pelvic region. The two radiosensitization protocols (a, b) allow a time interval between HBO and subsequent irradiation of 10-20 min. CONCLUSION: Recruitment of centers and patients is being strongly encouraged, detailed information is given on www.oxynet.org.     

Detection of dynamic stability deficits in subjects with functional ankle instability

PURPOSE: To determine which combination of landing protocol and analysis technique would be the most effective at detecting differences in dynamic stability between healthy subjects and subjects with functional ankle instability (FAI). METHODS: Fifty-eight subjects participated in this investigation: 29 healthy individuals and 29 individuals with FAI. Subjects were assessed during a single test session for time to stabilization (TTS) in the anterior/posterior, medial/lateral, and vertical directions from two protocols: a step down and jump protocol. The step down protocol started with each subject atop a 20-cm-high platform, and the jump protocol started with subjects in a standing position 70 cm from the center of a force plate and required each subject to jump off both legs and touch a designated marker placed at a position equivalent to 50% of the subject's maximum vertical leap. TTS scores in the anterior/posterior, medial/lateral, and vertical direction were compared between group, protocol, and type of analysis. RESULTS: A significant protocol by analysis by group interaction (F(1,56) = 6.9, P = 0.011) was observed for anterior/posterior TTS. Likewise, protocol by group (F(1,56) = 4.4, P = 0.042) and protocol by analysis (F(1,56) = 14.1, P < 0.001) interactions were also noted in anterior/posterior TTS. The jump protocol (2381.7 +/- 36.5 ms) produced significantly greater TTS scores in the vertical direction than the step protocol (1533.5 +/- 71.8 ms), whereas the unbounded third order polynomial (UTOP) method (2554.4 +/- 68.7 ms) produced significant greater TTS scores as compared with the sequential estimation (SE) method (1360.8 +/- 52.1 ms). CONCLUSIONS: The jump protocol and UTOP method of analysis are the most effective TTS combination in detecting differences between healthy and FAI groups.