Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status

B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin V(H) genes have better outcome than unmutated cases. V(H)-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, V(H) gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the V(H)-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining V(H) mutation status and telomere length, an improved subclassification of CLL was achieved identifying previously unrecognized patient groups with different outcomes.     

Metal artefact reduction in CT imaging of hip prostheses—an evaluation of commercial techniques provided by four vendors

Objective:

The aim of this study was to evaluate commercial metal artefact reduction (MAR) techniques in X-ray CT imaging of hip prostheses.

Methods:

Monoenergetic reconstructions of dual-energy CT (DECT) data and several different MAR algorithms, combined with single-energy CT or DECT, were evaluated by imaging a bilateral hip prosthesis phantom. The MAR images were compared with uncorrected images based on CT number accuracy and noise in different regions of interest.

Results:

The three MAR algorithms studied implied a general noise reduction (up to 67%, 74% and 77%) and an improvement in CT number accuracy, both in regions close to the prostheses and between the two prostheses. The application of monoenergetic reconstruction, without any MAR algorithm, did not decrease the noise in the regions close to the prostheses to the same extent as did the MAR algorithms and even increased the noise in the region between the prostheses.

Conclusion:

The MAR algorithms evaluated generally improved CT number accuracy and substantially reduced the noise in the hip prostheses phantom images, both close to the prostheses and between the two prostheses. The study showed that the monoenergetic reconstructions evaluated did not sufficiently reduce the severe metal artefact caused by large orthopaedic implants.

Advances in knowledge:

This study evaluates several commercially available MAR techniques in CT imaging of large orthopaedic implants.Images degraded by metal artefacts are a common problem in X-ray CT imaging. Artefacts caused by the presence of metallic implants in the CT scanned volume, such as hip prostheses or dental fillings, appear as dark and bright streaks across the reconstructed image. Metal artefacts can severely degrade the image quality and hence limit the diagnostic value of a CT scan.¹Hip prostheses cause severe artefacts when present in a CT scanned volume, and the resulting degradation of image quality leads to difficulties in diagnosing fractures, implant loosening or pathology in organs or soft tissue in the pelvic area. If CT images containing hip prostheses are used in radiotherapy treatment planning for tissue heterogeneity correction, the metal artefacts may introduce inaccuracies in dose calculations.Metal artefacts in CT imaging are mainly caused by beam hardening and photon starvation. Photon starvation artefacts are created when X-rays traverse materials with high attenuation coefficients, which leads to an insufficient amount of photons reaching the detectors and results in very noisy projections. The noise is magnified in the reconstruction process and the resulting streaks can be seen in the reconstructed image. Beam hardening refers to the fact that low-energy photons are attenuated to a greater degree than high-energy photons when passing through the scanned volume. This effect is more pronounced when the X-ray beam passes through high-density materials such as metals.¹In the past, several case-by-case solutions have been used in clinics to reduce metal artefacts. These are most often insufficient. One approach is to increase the tube peak voltage; however, this may only reduce metal artefact degradation to a minor degree and may not improve imaging of larger implants such as hip prostheses.² Increasing tube current, on the other hand, would lead to a higher radiation dose to the patient and may not have considerable impact on image quality either.² Approaches such as gantry tilting, or using lower attenuating materials in implants to avoid metal artefacts, may only be possible in specific situations and are effective to a limited extent.^3,4 Several proposed metal artefact reduction (MAR) algorithms working on raw projection data, such as modified iterative reconstruction (IR) methods and projection interpolation algorithms, have been shown to be a more general and effective technique for reducing artefacts.⁴Dual-energy CT (DECT) imaging enables image reconstruction from two energy sources and thereby creation of simulated monoenergetic images. This application makes it possible to obtain images as though they had been acquired with a monoenergetic high-energy beam, which would lead to reduction of metal artefacts caused by beam hardening.^5–9In addition to monoenergetic reconstructions in DECT, dedicated MAR algorithms have become available for clinical practice in the past couple of years. MAR algorithms in both single-energy CT imaging^10–14 and DECT imaging^8,9 have been shown to reduce metal artefacts.Some of the commercially available MAR techniques have previously been studied for several different clinical examples, ranging from artefacts created by smaller metallic objects such as dental fillings or screws to larger implants such as hip prostheses.^5–13 Monoenergetic images, reconstructed from DECT data, have been shown to enhance the diagnostic value of CT images containing orthopaedic implants.^5–10 Li et al¹² studied the application of a commercially available MAR algorithm in radiotherapy treatment planning and concluded that it improved CT number accuracy and structure visualization in CT images of orthopaedic implants. However, the improvement in CT number accuracy was shown not to have any significant clinical impact on photon dose calculations. A study by Andersson et al¹³ showed that the same MAR algorithm improves the accuracy in proton dose calculations.The aim of this study was to evaluate how the MAR techniques for CT scanners from four different vendors impact the diagnostic value of CT studies of hip prostheses, using a consistent experimental set-up for all machines. All CT images were evaluated in the same way, that is, by measuring CT number accuracy and noise in different regions of the images. Several scan parameters were varied to study their effect on MAR.     

Immune regulation by CD4+CD25+ T cells and interleukin-10 in birch pollen-allergic patients and non-allergic controls

BACKGROUND: CD4+CD25+ regulatory T (Treg) cells and the cytokines IL-10 or TGF-beta play key roles in the maintenance of T cell homeostasis and tolerance to infectious and non-infectious antigens such as allergens. OBJECTIVE: To investigate the regulation of immune responses to birch pollen allergen compared with influenza antigen by Treg cells obtained from birch pollen-allergic patients and non-allergic controls. METHODS: Peripheral blood was collected from 10 birch pollen-allergic patients and 10 non-allergic healthy controls. CD4+CD25+ and CD4+CD25- cells isolated by magnetic-activated cell sorting were co-cultured and stimulated with birch pollen extract or influenza vaccine in the absence or presence of anti-IL-10 or soluble TGF-betaRII. RESULTS: CD4+CD25+ cells from non-allergic controls were able to suppress influenza antigen and birch pollen stimulated effector cell proliferation, whereas CD4+CD25+ cells from allergic patients suppressed influenza antigen-, but not birch pollen-stimulated proliferation. The production of Th1 cytokines, but not Th2 cytokines, was suppressed by CD4+CD25+ cells from both allergic patients and controls, upon stimulation with birch pollen extract. Neutralization of IL-10 led to significantly increased production of IFN-gamma in cultures with CD4+CD25- T effector cells. In addition, six-fold higher concentrations of TNF-alpha were detected after neutralization of IL-10 in both CD4+CD25- and CD4+CD25+ cell cultures from allergic patients and controls. CONCLUSION: We demonstrate that the allergen-specific suppressive function of CD4+CD25+ cells from allergic patients is impaired compared with non-allergic controls. Moreover, neutralization of IL-10 enhances the production of TNF-alpha, suggesting counter-acting properties of IL-10 and TNF-alpha, where IL-10 promotes tolerance and suppression by Treg cells and TNF-alpha promotes inflammatory responses.     

99mTc-DTPA clearance measured by a dual head gamma camera in healthy subjects and patients with sarcoidosis. Studies of reproducibility and relation to bronchoalveolar lavage findings

99mTc-DTPA clearance was studied in ten healthy non smokers, five asymptomatic smokers and nine non smoking patients with sarcoidosis in the supine position with a dual head gamma camera allowing simultaneous information of regional clearance rates in frontal and dorsal projections. In the patients with sarcoidosis, a bronchoalveolar lavage was performed prior to the clearance study. DTPA clearance rate was measured during 60-90 min and data were corrected for recirculating radioactivity. The coefficients of variation for measurements on 2 consecutive days in the 10 healthy non smokers were 9%-11% for the right and left lung, anterior and posterior projections. The T1/2 calculated from total lung projections were 90-92 min for the anterior view and 84-85 min for the posterior view. Regional measurements did not add further information. No apico-basal difference was found but there was a significant fronto-dorsal gradient in 99mTc-DTPA clearance in the supine position. Smokers had significantly (P less than 0.01) faster clearance rates (T1/2 28 +/- 10 min) than healthy controls. In the sarcoidosis group clearance rates were increased in four patients and no relationships were found between DTPA clearance rates and inflammatory markers (lymphocytes, albumin, ACE) in the bronchoalveolar lavage fluid.     

Accelerated mobilization and formation of histamine in the gastric mucosa evoked by vagal excitation

1. The changes in the rate of histamine formation and in the histamine content of the parietal cell containing region of the gastric mucosa have been studied in rats under the influence of agents which evoke or abolish vagal excitation.2. The hypoglycaemia producing agents, insulin and 2-deoxyglucose (2-DG), raised the mucosal histamine-forming capacity (HFC) in a way similar to that previously observed on re-feeding, gastrin injection, and distension of the stomach wall.3. In cats, insulin injection elicited an elevation of mucosal HFC similar to the corresponding effect of insulin in rats.4. Hoechst 9980, which inhibits post-ganglionic cholinergic transmission, counteracted the elevation of mucosal HFC following vagal excitation, but did not inhibit changes produced by gastrin, thus indicating the absence of a cholinergic intermediary link between gastrin and changes in mucosal histamine.5. It is emphasized that although re-feeding, vagus excitation, gastrin and distension all produce similar changes in mucosal histamine, the clarification of the precise role of histamine as a natural stimulant for the parietal cells may require a fresh kind of approach.