Quantitative measurement of regional lung gas volume by synchrotron radiation computed tomography

The aim of this study was to assess the feasibility of a novel respiration-gated spiral synchrotron radiation computed tomography (SRCT) technique for direct quantification of absolute regional lung volumes, using stable xenon (Xe) gas as an inhaled indicator. Spiral SRCT with K-edge subtraction using two monochromatic x-ray beams was used to visualize and directly quantify inhaled Xe concentrations and airspace volumes in three-dimensional (3D) reconstructed lung images. Volume measurements were validated using a hollow Xe-filled phantom. Spiral images spanning 49 mm in lung height were acquired following 60 breaths of an 80% Xe-20% O2 gas mixture, in two anaesthetized and mechanically ventilated rabbits at baseline and after histamine aerosol inhalation. Volumetric images of 20 mm lung sections were obtained at functional residual capacity (FRC) and at end-inspiration. 3D images showed large patchy filling defects in peripheral airways and alveoli following histamine provocation. Local specific lung compliance was calculated based on FRC/end-inspiration images in normal lung. This study demonstrates spiral SRCT as a new technique for direct determination of regional lung volume, offering possibilities for non-invasive investigation of regional lung function and mechanics, with a uniquely high spatial resolution. An example of non-uniform volume distribution in rabbit lung following histamine inhalation is presented.     

Prostate Stem Cell Compartments : Expression of the Cell Cycle Inhibitor p27Kip1 in Normal, Hyperplastic, and Neoplastic Cells

The stem cells of rapidly renewing tissues give rise to transiently proliferating cells, which in turn give rise to postmitotic terminally differentiated cells. Although the existence of a transiently proliferating compartment has been proposed for the prostate, little molecular anatomical evidence for its presence has been obtained to date. We used down-regulation of the cyclin-dependent kinase inhibitor p27^Kip1 to identify cells capable of entering the proliferative phase of the cell cycle and, therefore, competent to fulfill the role of the transiently proliferating compartment. We examined the expression of p27^Kip1 in relation to its role in the development of prostatic carcinoma. Formalin-fixed paraffin-embedded specimens from matched samples of normal-appearing prostate tissue, benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, primary adenocarcinomas, and pelvic lymph node metastases were evaluated by comparative immunohistochemistry against p27^Kip1. In normal-appearing prostate epithelium, moderate to strong nuclear staining of p27^Kip1 was present in greater than 85% of the terminally differentiated secretory cells. The normal basal cell compartment, believed to contain prostatic stem cells, showed distinctive p27^Kip1 expression; acini in epithelial benign prostatic hyperplasia tissue contained more p27^Kip1-negative basal cells than acini from non-benign prostatic hyperplasia tissue. A third layer of cells was identified that was sandwiched between the basal cells and the luminal cells, and this layer was consistently p27^Kip1 negative. This intermediate layer was accentuated in the periurethral region, as well as in prostate tissue that had been subjected to prior combined androgen blockade. We hypothesize that, on appropriate additional mitogenic stimulation, cells in this layer, and other p27^Kip1-negative basal cells, are competent for rapid entry into the cell cycle. Consistent with the fact that cancer cells are capable of cell division, all cases of high-grade prostatic intraepithelial neoplasia and invasive carcinoma also showed down-regulation of p27^Kip1 as compared with the surrounding normal-appearing secretory cells. In pelvic lymph node metastases, p27^Kip1 expression was also reduced. In summary, our results suggest that lack of nuclear p27^Kip1 protein may delineate a potential transiently proliferating subcompartment within the basal cell compartment of the human prostate. In addition, these studies support the hypothesis that reduced expression of p27^Kip1 removes a block to the cell cycle in human prostate epithelial cells and that dysregulation of p27^Kip1 protein levels may be a critical early event in the development of prostatic neoplasia.     

Lack of coordination of nonverbal behaviour between patients and interviewers as a potential risk factor to depression recurrence: vulnerability accumulation in depression

BACKGROUND: Coordination of nonverbal behaviour during interactions is a prerequisite for satisfactory relationships. Lack of coordination may form a risk factor for depression. The 'vulnerability-accumulation hypothesis' assumes that vulnerability to recurrence of depression will increase with increasing experience of depressive episodes. Therefore it is expected that interviewers and patients remitted from a recurrent episode of depression would reach less coordination during a clinical interview compared to interviewers and patients remitted from a first lifetime episode. Moreover, we assumed that prior severity of depression modifies this reciprocal coordination process. METHODS: During discharge interviews, interviewers were videotaped in interaction with remitted patients with unipolar major depression recurrent depression (REC); n=28; first episode (SEP); n=22. Durations and frequencies of nonverbal involvement behaviour was registered during the first 15 min. Involvement of the patients consisted of gesticulating, looking at the interviewer, and general head movements; yes--nodding and hm, hm, yes, yes reflected involvement of the interviewer. Coordination between patients and interviewers was analyzed per 3-min epochs and defined as 'attunement': the absolute difference between patients' and interviewers' involvement. Averaged attunement, its time course and variability (presumably reflecting control of the attunement process) were assessed. RESULTS: The time course of nonverbal attunement differed between the REC and SEP condition. A larger variability of attunement was found in patients remitted from a relatively severely depressed episode, compared to patients remitted from a severe first life time episode. No other significant differences were found. CONCLUSIONS: Partial support was found for the notion that nonverbal vulnerability accumulates in depression and that the severity of prior depression modifies this process.     

Development and evaluation of NucliSens basic kit NASBA for diagnosis of parainfluenza virus infection with 'end-point' and 'real-time' detection

New methods for the detection of human parainfluenza viruses (HPIVs) were developed. These were based on nucleic acid sequence-based amplification (NASBA) and utilised the NucliSens Basic Kit. Primers and probes were selected from the haemagglutinin neuraminidase (HN) gene of HPIV1, HPIV2 and HPIV3, and from the phosphoprotein (P) of HPIV4a and -4b. Synthetic RNA, titrated control virus stocks and respiratory specimens (n=44) were utilised to evaluate performance of the assays. Detection of NASBA products was by probe hybridisation and electrochemiluminescence (ECL) ('end-point' detection) or using molecular beacons ('real-time' detection). The assays using ECL detection proved to be both sensitive and specific. Typically, less than or equal to 100 RNA copies or one TCID(50) input was detectable with no cross-reaction between the specific HPIV assays and other respiratory viruses. Results for clinical samples were concordant with those obtained by 'conventional' procedures by classical viral diagnostic methods. 'Real-time' detection utilised probes specific for either HPIV1 or HPIV3 with similar performance characteristics to the assays with 'end-point' detection. The feasibility of multiplexing targets together was confirmed using a combined HPIV1 and HPIV3 assay with good results for ECL and molecular beacon detection on control material and clinical samples.     

Left ventricular outflow tract obstruction associated with chronic ventricular assist device support

Favorable long-term patient outcome after insertion of a left ventricular assist device (LVAD) as a bridge to recovery or destination therapy for the treatment of end-stage cardiomyopathy is adversely affected by pathophysiologic changes affecting the heart. Alterations in the native aortic valve apparatus, specifically aortic valve cusp fusion, is an example of such a phenomenon and may especially affect patients in cases of bridge to recovery, a rare but reported event. A retrospective review of the last 33 LVAD placements at our institution was conducted, including reviews of operative reports and pathologic examinations of the native hearts. Seven hearts were found to have varying degrees of aortic valve cusp fusion after chronic LVAD support (63-1, 339 days). Five of these patients had native aortic valves, and two had bioprosthetic valves. The left ventricular outflow tracts in two patients were surgically occluded at the time of LVAD insertion. Aortic valve cusp fusion occurs in roughly 25% of patients on chronic LVAD support. This phenomenon may prove to be clinically significant by creating a potential source of emboli and infection. In addition, in the case of myocardial recovery, left ventricular outflow tract obstruction could limit parallel flow and produce suprasystemic ventricular pressures that in turn would elevate left ventricular end diastolic pressures. The latter may contribute to further myocardial injury, ultimately limiting the ability of an otherwise recovered heart to be weaned from LVAD support.     

A mathematical simulation of the AIDS patient and extracorporeal detoxification

A simple numerical simulation of AIDS patient detoxification by a hypothetical extracorporeal device for the removal of viruses, infected white cells, and syncytia has been designed. The mathematical model accounts for healthy blood white cells attacking and destroying the viruses, while at the same time the viruses attack and infect certain white cells. The infected white cells serve as a site for viral growth; eventually the cells lyse, releasing a large number of viruses into the blood stream. The healthy white cells and infected white cells combine to form syncytia, where the virus multiplies, and finally the syncytium ruptures releasing all the virus. This model can be used to predict concentrations over a specified period for the patient. This is a mathematical model to be used as a research and design tool only.     

Markers in HIV associated tuberculosis in Kenya

Tuberculosis is one of the most frequent opportunistic infections in HIV-infected patients in developing countries. In some instances, manifestations of pulmonary tuberculosis precede all other HIV related signs and symptoms because of the high virulence of M. tuberculosis. In order to characterise the interaction between these two pathogens, clinical and immunological parameters in pulmonary tuberculosis patients with and without HIV infection were compared. Amongst newly diagnosed pulmonary tuberculosis patients the association of some of these changes with the clinical outcome were evaluated. Of these, 44% were co-infected with HIV. Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone, P= 0.0292. Low CD4+ lymphocyte counts, lymphadenopathy and BCG scar absence could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients.     

Measuring homelessness and residential stability: The residential time‐line follow‐back inventory

Reliable and valid longitudinal residential histories are needed to assess interventions to reduce homelessness and increase community tenure. This study examined the test‐retest reliability, sensitivity to change, and concurrent validity of the Residential Time‐Line Follow‐Back (TLFB) Inventory, a method used to record residential histories in the Collaborative Program to Prevent Homelessness (n = 1,381). The Residential TLFB Inventory yielded temporally stable aggregate measures of duration in residential categories, and it revealed significant differences in change over time when contrasting study groups. A comparison of agency and participant data at one site.     

Stability of a mobile electron linear accelerator system for intraoperative radiation therapy

The flexibility of mobile electron accelerators, which are designed to be transported to an operating room and plugged into a normal 3-phase outlet, make them ideal for use in intraoperative radiation therapy. However, their transportability may cause trepidation among potential users, who may question the stability of such an accelerator over a period of use. In order to address this issue, we have studied the short-term stability of the Mobetron system over 20 daily quality assurance trials. Variations in output generally varied within +/-2% for the four energies produced by the unit (4, 6, 9, and 12 MeV) and changes in energy produced an equivalent shift of less than 1 mm on the depth-dose curve. Hours of inactivity, with the Mobetron powered on for use either throughout the day or overnight, led to variations in output of about 1%. Finally, we have tested the long-term stability of the absolute dose output of the Mobetron, which showed a change of about 1% per year.