Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease.

OBJECTIVE: TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. MATERIALS AND METHODS: TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with (3) H-thymidine incorporation and propidium iodine staining. RESULTS: TRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression-free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes in vitro. CONCLUSIONS: We show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.

A closer look at non-Hodgkin's lymphoma cases in a national Swedish systemic lupus erythematosus cohort: a nested case-control study.

OBJECTIVE: To investigate risk factors for non-Hodgkin's lymphoma (NHL) and analyse NHL subtypes and characteristics in patients with systemic lupus erythematosus (SLE). METHODS: A national SLE cohort identified through SLE discharge diagnoses in the Swedish hospital discharge register during 1964 to 1995 (n = 6438) was linked to the national cancer register. A nested case control study on SLE patients who developed NHL during this observation period was performed with SLE patients without malignancy as controls. Medical records from cases and controls were reviewed. Tissue specimens on which the lymphoma diagnosis was based were retrieved and reclassified according to the WHO classification. NHLs of the subtype diffuse large B cell lymphoma (DLBCL) were subject to additional immunohistochemical staining using antibodies against bcl-6, CD10 and IRF-4 for further subclassification into germinal centre (GC) or non-GC subtypes. RESULTS: 16 patients with SLE had NHL, and the DLBCL subtype dominated (10 cases). The 5-year overall survival and mean age at NHL diagnosis were comparable with NHL in the general population-50% and 61 years, respectively. Cyclophosphamide or azathioprine use did not elevate lymphoma risk, but the risk was elevated if haematological or sicca symptoms, or pulmonary involvement was present in the SLE disease. Two patients had DLBCL-GC subtype and an excellent prognosis. CONCLUSIONS: NHL in this national SLE cohort was predominated by the aggressive DLBCL subtype. The prognosis of NHL was comparable with that of the general lymphoma population. There were no indications of treatment-induced lymphomas. Molecular subtyping could be a helpful tool to predict prognosis also in SLE patients with DLBCL.

Association analysis with microsatellite and SNP markers does not support the involvement of BCL-2 in systemic lupus erythematosus in Mexican and Swedish patients and their families.

We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2.

Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjögren's syndrome and systemic lupus erythematosus.

OBJECTIVE: To investigate the occurrence of IgA autoantibodies to Ro 52 kDa, Ro 60 kDa and La antigen in serum of patients with primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). METHODS: Recombinant Ro 52 kDa, Ro 60 kDa and La antigens were used to analyse autoantibodies in serum from 25 patients with pSS, 30 patients with SLE and 20 controls using a semiquantitative immunoblotting approach. RESULTS: Among the patients with pSS, 21 (84%) had detectable IgA autoantibodies to Ro 52 kDa, 13 (52%) to Ro 60 kDa and 20 (80%) to La antigen. The corresponding results for the patients with SLE were 22 (73%), 14 (47%) and 20 (67%), respectively. No IgA autoantibodies against the three antigens were detected in 20 normal controls. A comparison of several clinical features with the titres of IgA antibodies to Ro 52 kDa, Ro 60 kDa and La, revealed a significant relation between IgA anti-Ro 52 and IgA anti-La to sicca (p< 0.05). Semiquantitative data suggest that IgG is the dominating antibody to the three antigens followed by IgM > IgA in both SLE and pSS patients. Specificity studies of IgA autoantibodies with different subfragments of Ro 52 kDa and Ro 60 kDa antigens showed that IgA antibodies did not differ from IgG and IgM in their recognition pattern. CONCLUSION: These results suggest that besides IgM and IgG, IgA autoantibodies are also detected at high frequency in patients with pSS and SLE. Further studies are necessary to evaluate the contribution of these IgA autoantibodies to inflammation as well as their diagnostic value.

Risk evaluation and patient assessment in sedation.

Risk assessment gives a good clinical guide to the understanding of our patients' medical problems. The dentist can cope with problems related to patients belonging to risks group 1 and 2, but not to groups 3 or 4. The results of studies on risks, morbidity, and mortality in anaesthesia teach us that the human factor and technical error provoke complications, morbidity and mortality, seemingly unnecessarily. Case history and a simple physical examination, primarily concentrated on respiration and circulation, are of greatest importance. Main risks during conscious sedation are regurgitation and aspiration of fluid and smaller objects, such as a broken dentist's drill or a cardiac complication. Most feared is the risk of a reinfarcation. The aim of sedation is to reduce anxiety and restlessness. Of greatest importance is thorough patient information and a good doctor-patient contact.

Analysis of a system for ultrasonic imaging of attenuation and texture in soft tissue.

Attenuation in tissue decreases both the amplitude and the bandwidth of a reflected ultrasonic signal. Only the amplitude is restored in conventional ultrasonic equipment by amplifying the signal in a time-gain-compensator. This paper describes a method for restoring both the amplitude and bandwidth of the signal and an implemention of this method is proposed. This consists of two main parts: a device for estimating the attenuation and a time-variable circuit. The time-variable circuit is controlled by the estimated attenuation such that its transfer function approximates the inverse of the transfer function of the attenuation within the transducer passband. Its output is then almost independent of the attenuation and contains information on the texture of the tissue. Both the texture and attenuation estimates are displayed graphically. The quality of the image of the texture can be improved by choosing a wideband transducer, since it is almost exclusively dependent of transducer bandwidth.

Lidocaine and amitriptyline interaction during experimental haemoperfusion.

Displacement of amitriptyline by lidocaine was studied during haemoperfusion (HP) in five beagle dogs. Clearance of amitriptyline during HP was 0.93, although the amount of amitriptyline removed was only 2% of the given dose. Lidocaine does therefore not improve amitriptyline yield during HP. Clearance of lidocaine during HP was 0.99. Almost 13% of the lidocaine given intravenously was removed by HP. Lidocaine did not improve myocardial performance during HP in amitriptyline-intoxicated dogs. At necropsy the highest concentrations of amitriptyline in this model were found in the brain and the lung. The amitriptyline/nortriptyline ratio was lowest in the liver and lung, suggesting that these two organs are major sites of metabolism.

An oxygen-consuming model lung for evaluation of anaesthetic circuits.

We have constructed an oxygen-consuming model lung based on pure combustion of hydrogen. Besides consuming oxygen the model produces water vapour, and carbon dioxide is delivered to the lung, thus mimicking carbon dioxide production. Oxygen consumption and carbon dioxide production can be set at desired values. The model lung can be used for investigations on and evaluation of all types of anaesthesia circuits. Results in a circle system with carbon dioxide absorption show that FIO2 is related to the fresh gas flow. The end tidal CO2 level is correlated to the alveolar ventilation and cannot be used for predicting FIO2.

Thoracic gas volume and chest-abdomen dimensions during anesthesia and muscle paralysis.

The aim was to study thoracic gas volume (TGV) in anesthetized and paralyzed subjects (n = 16) and to analyze any change in TGV in terms of thoraco-abdominal dimensions. TGV was measured by means of a body plethysmograph, using a super syringe for lung inflation during muscle paralysis. The thoraco-abdominal shape at the mamillary and umbilical levels was studied by means of magnetometry for the assessment of antero-posterior diameters (A-P), a strain gauge technique for measuring circumferences and respiratory inductive plethysmography for the recording of cross-sectional areas. TGV was reduced by an average of 28 per cent, from 2.38 1 awake to 1.72 1 during pentothal anesthesia and spontaneous breathing. No change in A-P diameters or cross-sectional areas were noticed. Muscle paralysis and mechanical ventilation caused no further change in TGV, nor were there any changes in A-P diameters, circumferences or cross-sectional areas of the chest or abdomen. The rib cage contribution to the tidal breath was significantly increased, from 41 per cent to 62 per cent to the tidal volume. The result of a lowered TGV during anesthesia concurrently with no measurable change in chest-abdomen dimensions remains a paradox not yet fully understood.

Studies on pulmonary function in patients during respiratory treatment. Diagnostic and prognostic evaluations.

Twenty-nine patients, divided into three groups: 1) chronic obstructive pulmonary disease; 2) acute or chronic pulmonary disease with left heart failure; 3) respiratory insufficiency after peritonitis, pancreatitis, and/or sepsis, were studied during respirator treatment with regard to gas exchange, breathing mechanics and central circulation. The dead space ventilation was somewhat greater in group 1 than in the other groups. The alveolar-arterial oxygen tension difference was least in group 1, greater in group 2 and extremely high in group 3. Neither dynamic compliance of the thorax nor inspiratory resistance showed any significant differences between the groups. The cardiac output had the highest values in group 3. The venous admixture was generally small in group 1 and extremely large in group 3. The pulmonary artery pressures were highest in group 2. Three variables proved to be valuable when assessing the prognosis of a patient: a large venous admixture; a large alveolar-arterial oxygen tension difference, and a high pulmonary artery pressure indicated a less favourable prognosis.

Chest wall mechanics during artificial ventilation.

Chest wall mechanics were studied in six healthy volunteers before and during anesthesia prior to surgery. The intratracheal, esophageal, and intragastric pressures were measured concurrently. Gas flow was measured by pneumotachography and gas volume was obtained from it by electrical integration. Rib cage and abdomen movements were registered with magnetometers, these being calibrated by "isovolume" maneuvers. During spontaneous breathing in the conscious state, rib cage volume displacement corresponded to 40% of the tidal volume. During anesthesia and artificial ventilation, this rose to 72% of the tidal volume. The relative contributions of rib cage and abdomen displacements were not influenced by a change in tidal volume. Compliance was higher with a larger tidal volume, a finding which could be due to a curved pressure-volume relationship of the overall chest wall.