Soft x-ray Ar + 8 laser excited by low-voltage capillary discharge.

We demonstrated the operation of a 46.9-nm capillary discharge Ar + 8-laser excited by electrical pulses at a very low voltage (35 - 45 kV), which is approximately two times lower than previously reported. The decrease in pulse voltage not only allows for further reduction in the size of the laser's excitation part, but also a principal shift to the experimental methods, techniques, and technologies used in ordinary pulsed gas lasers operating in the ultraviolet, visible, and infrared regions of the spectra. In an argon-filled alumina capillary with an inner diameter of 3.1 mm and a length of 22 cm, laser pulses with an energy of 4 µJ and a duration of 1.6 ns were generated. The laser produces a beam with a Gaussian intensity distribution and an FWHM divergence of 1.9 mrad. The results could be particularly useful in the development of compact, practical soft x-ray capillary lasers for use in small laboratories at educational and research institutions.

What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome.

Background: Glioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15-16 months and 5-year survival rate 5%-10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time. Methods: We identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented. Results: Median overall survival was 1.07 years, which was significantly longer than in the 2004-2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR = 1.89, p < 0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0-1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities. Conclusion: The median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.

Prognostic factors for glioblastoma patients--a clinical population-based study.

OBJECTIVES: To address in a retrospective and population-based study prognostic factors for survival time after diagnosis and surgery for glioblastoma multiforme (GBM). MATERIAL AND METHODS: During the study period, 430 patients were identified at the multidisciplinary team conferences as newly diagnosed GBM, 201 of these were considered not to benefit from surgery, and thus, a total of 229 consecutive adult patients with GBM were operated between January 2004 and December 2008 at Sahlgrenska University Hospital and were retrospectively analyzed. Potential predictors of survival were statistically analyzed using Poisson regression models. RESULTS: Median survival was 0.73 years. Multivariable analysis showed the following factors to positively influence survival: younger age at surgery, secondary tumor genesis, unifocal tumor location (vs multifocal), resection (vs biopsy only), radiotherapy, and combination of radiotherapy and chemotherapy. CONCLUSION: This population-based study supports the importance of surgery instead of biopsy only, followed by radiotherapy and chemotherapy, a finding which has also been stated in earlier non-population-based reports. However, it is obvious that the solution is not just surgical radicality followed by optimal oncological treatment. It is of great importance to seek further subclassifications, biomarkers, and new treatment modalities to make a significant change in survival for individuals.

Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene.

The serum concentration of mannose-binding lectin (MBL) is genetically determined by a series of allelic polymorphisms in the MBL2 gene. Since several polymorphisms of the MBL2 gene have been suggested to be risk locus for systemic lupus erythematosus (SLE), we investigated MBL2 polymorphisms in 315 SLE patients from Hungary and 182 geographically matched healthy controls. Within the group of patients, we found that homozygotes for an MBL2 down-regulating promoter polymorphism at position -221 (YA to XA) (rs7096206) were significantly (p=0.017) younger at diagnosis than the other patients. The frequency of juvenile-onset SLE (

Low levels of antibodies against E. coli and mycobacterial 65kDa heat shock proteins in patients with inflammatory bowel disease.

OBJECTIVE AND DESIGN: The aim of the present study was to support and extend our initial observation, where we found low levels of antibodies against mycobacterial 65kD heat shock proteins in patients with inflammatory bowel disease (IBD). For this purpose we tested a new group of 124 patients with IBD, and beside measuring antibodies to Mycobacterium bovis 65kD heat shock protein (Hsp65) and human 60kD heat shock protein (Hsp60) as described previously, we also determined IgG antibody levels to Hsp65 from E. coli, called GroEL. PATIENTS AND CONTROL SUBJECTS: seventy-four patients with Crohn's disease (CD) (30 males, 44 females, 33 (27-45) years old, median (interquartile range)) and 50 patients with ulcerative colitis (UC) (22 males, 28 females, 38 (30-50) years old) were involved in the study. 110 healthy subjects (34 males, 76 females, 47 (37-53) years old) served as controls. Study subjects were consecutive patients referred to an IBD center for complex treatment of the disease. Methods and statistical analysis: The amounts of IgG-type antibodies reacting with proteins of the chaperonin 60 family were assessed by ELISA. Since the antibody levels to heat-shock proteins as variables were not normally distributed, non-parametric Mann-Whitney test and Dunn post hoc test were used for group comparisons. RESULTS: Median levels of anti-GroEL (7,5 (3,5-18,3)) and anti-Hsp65 (4,8 (2,1-7,85)) were significantly (GroEL p = 0,008; and Hsp65 p < 0,001) lower in the IBD patients than in the healthy subjects (GroEL: 10,0 (5,4-31,0); Hsp65: 7,04 (4,66-12,77)). However this difference was found to be restricted to the CD patients (GroEL: 7,5 (3,7-14,2); p < 0,05; Hsp65: 4,35 (1,90-6,94); p < 0,001). We did not find difference in the concentration of anti-human Hsp60 IgG levels between patients (Hsp60: 45,5 (24,9-69,0)) and healthy controls (38,4 (21,6-69,4). Regarding the serum concentrations of each antibody tested there was no significant difference between the active and inactive stage of disease. CONCLUSION: Our present findings support conclusion of our previous work, antibody levels not only for Mycobacterium bovis hsp65 but for E. coli GroEl were found to be decreased as well. In contrast no changes in the concentrations of human anti-hsp60 antibodies were observed. These findings indicate that production of antibodies to 65 kDa bacterial heat shock proteins is selectively impaired in IBD.

Sex hormones in hereditary angioneurotic oedema.

OBJECTIVE: The fluctuations in sex hormone levels at the beginning of adolescence, in the perimenopausal period, during pregnancy or during the use of oral contraceptives can precipitate oedematous attacks in hereditary angioneurotic oedema (HANO). Attacks usually disappear after the onset of menopause. This study was undertaken to establish any relationship between the serum levels of sex hormones and the incidence of HANO attacks. PATIENTS AND MEASUREMENTS: Serum levels of LH, FSH, progesterone, oestradiol, testosterone, PRL and SHBG were measured in 78 patients [mean age 30.3 years (range 4-70 years)] with HANO. A questionnaire was used to explore the medical history of adult patients to characterize the evolution and the characteristics of attacks. RESULTS: The number of attacks was significantly higher [odds ratio (OR) 6.36 (1.31-30.81); P = 0.022] in females with high progesterone levels (> or = 4 nmol/l), irrespective of age, menstrual cycle and danazol dose. The OR was even higher [13.4 (2.2-81.4); P = 0.005] when only subcutaneous attacks were considered. Multiple logistic regression analysis demonstrated a significantly lower attack frequency during 1-year follow-up in patients with a higher (40 nmol/l) SHBG level (OR 0.25 (0.07-0.90); P = 0.034). This difference existed independently of age and danazol dose. CONCLUSION: In view of these results, the monitoring of progesterone and SHBG levels can prove useful in the prediction of attacks in hereditary angioneurotic oedema.

High prevalence of IgG and IgA antibodies to 19-kDa Helicobacter pylori-associated lipoprotein in chronic urticaria.

BACKGROUND: Chronic urticaria has been described in patients with Helicobacter pylori infection. We studied the titer of IgG and IgA type antibodies against H. pylori in patients with and without urticaria of unknown etiology. We also investigated the prevalence of antibodies against H. pylori-associated lipoprotein 20 (lpp20) in patients with and without chronic urticaria. METHODS: The concentration of anti-H. pylori antibodies (IgG and IgA) was determined by the RIDA test. The level of anti-lpp20 antibodies was determined by Western blot using various H. pylori antigens (from 19 to 120 kDa). RESULTS: Patients with chronic urticaria and H. pylori infection (subgroup 1, n = 33) had high IgG and IgA titers whereas all patients with chronic urticaria and without H. pylori infection (subgroup 2, n = 23) were seronegative (P = 0.0128 for IgG and P = 0.003 for IgA). Titers in subgroup 1 did not differ significantly from a control group (n = 33) with severe H. pylori-associated gastritis without urticaria. The prevalence of the anti-lpp20 antibodies was significantly higher in subgroup 1 compared to the control group (93.9 vs 21.2%, P < 0.0001 for IgG, and 46.1 vs 6.3%, P < 0.0029 for IgA). CONCLUSIONS: We suggest that IgG and IgA antibodies to H. pylori-associated lpp20 may play role in the pathogenesis of chronic urticaria.

Acute abdominal attack of hereditary angioneurotic oedema associated with ultrasound abnormalities suggestive of acute hepatitis.

UNLABELLED: Hereditary angioneurotic oedema (HANO) is an autosomal dominant disorder caused by a deficiency of the inhibitor protein Cl-esterase. Recurrent subcutaneous and/or submucosal oedema formation is a hallmark of this disease. HANO is a rare, but potentially life-threatening disorder with a mortality around 20-30%. Acute oedematous abdominal attacks of HANO can mimic a surgical emergency; this is exemplified by the case of a 14-y-old male patient with HANO admitted for such clinical manifestations. CONCLUSION: Diagnostic clues include ascites and abnormalities of hepatic structure visible with ultrasound during the oedematous attack. The importance of appropriate treatment is emphasized.

The effect of heat-inactivated Helicobacter pylori on the blastogenic response of peripheral blood mononuclear cells of patients with chronic urticaria.

BACKGROUND: Helicobacter pylori, the most important etiologic factor of gastritis and peptic ulcer, has recently been associated with several extradigestive diseases. Previous studies reported conflicting results on H. pylori eradication in chronic urticaria, in that some studies showed a benefit, while others found no effect. METHODS: Peripheral blood mononuclear cells of 24 chronic urticaria patients (13 seropositive/11 seronegative for H. pylori) and 18 healthy controls (9 seropositive/9 seronegative) were stimulated with whole heat-inactivated H. pylori (8 x 10(5), 8 x 10(6 )and 8 x 10(7) bacteria/well), phytohemagglutinin (2 microg/ml) and pokeweed mitogen (5 microg/ml). The proliferative response was determined by (3)H-thymidine incorporation. Helicobacter-specific IgG antibody response was determined by ELISA. RESULTS: There were significantly higher proliferative responses to various concentrations of whole heat-inactivated H. pylori antigen in 6- to 7-day cultures of peripheral blood mononuclear cells of chronic urticaria patients compared to healthy controls. We found a tendency to exhibit a higher proliferative response to either Helicobacter antigens or mitogens in seropositive compared to seronegative patients. CONCLUSION: Our results support the hypothesis that there is an increased lymphocyte reactivity in chronic urticaria, perhaps further enhanced by the presence of H. pylori which, therefore, may be involved as a trigger in the pathogenesis of chronic urticaria.

Eradication of Helicobacter pylori and improvement of hereditary angioneurotic oedema.

Helicobacter pylori infection is thought to be a causal factor in various dermatological disorders. We assessed the frequency of H pylori infection in 65 patients with hereditary angioneurotic oedema. We measured the serum concentration of antibodies against H pylori and did the carbon-14-urease breath test in patients with positive H pylori serology. 19 of 65 patients had H pylori infection. All patients with infection, and 11 of 46 without infection, had a history of recurrent episodes of acute abdominal pain. We successfully eradicated H. pylori infection in 18 patients. The frequency of abdominal symptoms was significantly higher in the infected group (p=0.002 after adjustment for age). In nine of 19 patients with dyspepsia, the frequency of oedematous episodes decreased from 100 over 10 months before eradication to 19 during the 10-month follow-up period. Screening for, and eradication of, H pylori infection seems to be justified in patients with hereditary angioneurotic oedema.

Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema.

BACKGROUND: Hereditary angioneurotic oedema (HAE) is a rare cause of ascites. As acute abdominal attacks of the disease can mimic surgical emergencies, prompt and accurate diagnosis is essential. This study was undertaken to evaluate the usefulness of serial abdominal ultrasound (US) examinations. PATIENTS AND METHODS: Seventy patients with HAE were followed up for almost a decade. All patients presenting with an acute oedematous attack underwent abdominal US, which was then repeated 24 and 48 h after appropriate therapy. RESULTS: Twenty-two acute oedematous attacks with abdominal complaints severe enough to justify hospital admission occurred in the study population. Abdominal US performed during the attack showed oedematous thickening of the intestinal wall in 80% of cases and invariably demonstrated the presence of free peritoneal fluid in all patients. Rapid symptomatic relief achieved by treatment was accompanied by the significant regression of US abnormalities. CONCLUSIONS: Transitory ascites demonstrated by abdominal US is a clue to the diagnosis of an acute abdominal attack of HAE. The possibility of HAE should always be considered whenever unexplained abdominal pain recurs with or without ascites.

Angiooedema due to acquired deficiency of C1-esterase inhibitor associated with leucocytoclastic vasculitis.

A hereditary and an acquired type of C1-esterase inhibitor deficiency have been described. Manifestations characteristic of both forms include recurrent subcutaneous and submucosal angiooedema. Acquired C1-esterase inhibitor deficiency has been observed in association with lymphoproliferative disorders, malignancy, autoimmune diseases and infections. We report on a case with the acquired form of the disease accompanied by leucocytoclastic vasculitis. Treatment with antimalarial agents resulted in complete resolution of symptoms and signs. Furthermore, C1-esterase inhibitor concentration and activity, as well as C1 levels, all returned to normal.

Comparative study on antibodies to human and bacterial 60 kDa heat shock proteins in a large cohort of patients with coronary heart disease and healthy subjects.

BACKGROUND: Recent observations indicate an association between antibodies against mycobacterial heat shock protein (hsp65) and coronary heart disease (CHD). Previously, we reported on marked differences in antigen specificity and complement activating ability of anti-hsp65 antibodies and auto-antibodies against human heat shock protein, hsp60. Here, we investigated whether there are differences between antih-sp65 and anti-hsp60 antibodies in their association with CHD. DESIGN: We measured by ELISA the levels of antibodies to hsp65, hsp60 and E. coli-derived GroEL in three groups: Group I, 357 patients with severe CHD who underwent by-pass surgery; Group II, 67 patients with negative coronary angiography; Group III, 321 healthy blood donors. Antibodies against Helicobacter pylori were also measured by commercial ELISA. RESULTS: As calculated by multiple regression analysis, the levels of anti-hsp60 auto-antibodies were significantly higher in Group I compared to Group II (P = 0.007) or Group III (P < 0.0001). By contrast, although concentrations of anti-hsp65 and anti-GroEL antibodies in Group I were higher than in Group III, no significant differences between Group I and Group II were found. Antibodies to the two bacterial hsp strongly correlated to each other, but either did not correlate or weakly correlated to hsp60. In Group I, serum concentrations of anti-H.pylori antibodies significantly correlated with those of anti-hsp65 and anti-GroEL antibodies but they did not correlate with the anti-hsp60 antibodies. CONCLUSIONS: As to their clinical relevance, a remarkable difference become evident between antibodies to human hsp60 and antibodies against bacterial hsp in the extent of association with CHD. On the basis of these findings and some pertinent literature data, an alternative explanation for the association between high level of anti-hsp antibodies and atherosclerotic vascular diseases is raised.

Levels of antibodies against C1q and 60 kDa family of heat shock proteins in the sera of patients with various autoimmune diseases.

Previously a strong positive correlation was found between antibodies to C1q (C1qAb) and antibodies against human heat shock protein (hsp60) and mycobacterial hsp65 in HIV infected patients. Here the levels of these antibodies were measured in the sera of patients with different autoimmune diseases (122 systemic lupus erythematosus (SLE), 55 systemic sclerosis, 33 undifferentiated connective tissue disease (UCTD), 27 primary Raynaud syndrome, 21 rheumatoid arthritis (RA), 14 polymyositis/dermatomyositis (PM/DM), and 192 healthy blood donors. The prevalence of IgG C1qAb was found to be high (P<0.0001 as compared to the healthy controls) only in the SLE group. The levels of the anti-hsp60 (P=0.0094) and anti-hsp65 (P=0.0108) antibodies were high only in the UCTD patients. No correlation was found between the C1qAb and anti-hsp antibodies in any group except a significant (P=0.011) positive correlation between C1qAb and hsp65 antibodies in the patients with UCTD. These findings indicate that the autoantibodies against C1q are heterogeneous: in different diseases different types of C1qAb may dominate.

High levels of antibodies against Clq are associated with disease activity and nephritis but not with other organ manifestations in SLE patients.

OBJECTIVE: Serum concentration of antibodies to C1q (C1qAb) has been reported to be elevated in a high percentage of patients with systemic lupus erythematosus (SLE). The associations of high C1qAb levels with different clinical manifestations and the activity of the disease, however, are not definitely understood. METHODS: We measured the levels of IgG type C1qAb in the sera of 137 patients with SLE using an ELISA method. RESULTS: Serum concentrations of C1qAb were found to be higher (p < 0.0001) in SLE patients than in healthy controls. High titer (> 66 AU/ml) C1qAb was found in 40/137 (29.2%) SLE patients, and 4/192 (2.1%) healthy controls (p < 0.0001). A strong negative correlation (R = -0.4, p < 0.0001) between the age of the patients and the C1qAb titers could be detected. C1qAb levels in clinically active SLE patients significantly (p < 0.0001) exceeded those measured in the sera of patients in the inactive stage of the disease. A significant positive correlation was detected between C1qAb levels and the laboratory activity markers (anti-DNA, low C3 level) of the disease. We found a significant negative correlation between levels of C1qAb and a negative acute phase protein, alpha2-HS-glycoprotein. Renal involvement was present in 11/40 (27.5%) and 11/97 (11%) of the patients with high and low titers of C1qAb, respectively (p = 0.038). The prevalence of other organ manifestations was, however, the same in the patients with or without high titer C1qAb. CONCLUSION: These findings indicate that C1qAb measurement is a useful method for detecting the activity of SLE and predicting renal manifestations, but not other organ involvement in the disease.

IgE-containing cells in gastric mucosa with and without Helicobacter pylori infection.

Gastric mucosa responds with inflammation to Helicobacter pylori (H. pylori) infection. While numerous reports have shown that the immune system produces specific IgG, IgA, and IgM isotype anti H. pylori antibodies, IgE-mediated pathways of H. pylori-associated gastritis are mostly unknown. Our aim was to evaluate whether an increased presence of IgE in the antral gastric mucosa is responsible for the severity of the H. pylori-associated gastritis. The number of IgE-containing cells was estimated in formalin-fixed, paraffin-embedded antral gastric biopsy specimens using immunohistochemistry in three groups of patients: (i) 20 H. pylori-positive cases with moderate inflammation, (ii) 19 H. pylori-negative cases with moderate inflammation, and (iii) 19 H. pylori-negative cases with normal mucosa. In chronic gastritis, the number of IgE-positive cells increased significantly as compared to normal mucosa. In gastritic patients, H. pylori positivity was accompanied by a significant accumulation of IgE-positive cells, mainly plasma cells. These data suggest that IgE-mediated immune response probably plays an important role in the development of H. pylori-associated gastritis.

Inhibition of IgE production by epsilon (epsilon) chain-specific antisense oligonucleotides (AOs) studied on human myeloma cell line U266 and peripheral blood mononuclear cells of a patient with hypereosinophilia.

Based on cDNA sequence data epsilon chain-specific antisense oligonucleotides were synthesized and checked on in vitro IgE production. Using peripheral blood cells from a hypereosinophilic patient and a human IgE myeloma cell line, U266, marked reduction of in vitro IgE production measured by PRIST was observed. The effect of epsilon antisenses proved to be isotype specific since IgG production by both peripheral blood cells and a lymphoma cell line, CESS, was not affected. Moreover, the expression of other markers on U266 (interleukin-6 receptor and gp130) were not influenced by epsilon-specific antisense oligonucleotides.