[Epidemiology of corticosteroid-induced osteoporosis].
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Anti-Inflammatory Agents↗
Biomedical subjects
J Braun
Publications and source records attributed to J Braun.
Comparison of colonic J-pouch reconstruction and straight coloanal anastomosis after intersphincteric rectal resection.
The tendency towards sphincter-preserving resection for distal rectal cancers has led to the technique of straight coloanal anastomosis (CAA) and colonic J-pouch anal anastomosis (CPA) after low anterior resection. The aim of the present study was to compare complication rate, anorectal physiology and functional results after both types of reconstruction after ultra-low intersphincteric resection. A total of 31 patients who had undergone CPA were followed up prospectively using anorectal manometry and a standardised questionnaire and were compared with 63 patients who had undergone CAA and were followed up in the same way. The complication rate after CPA did not differ significantly from that after CAA. One year postoperatively, the median stool frequency and urgency were reduced after CPA (1.7+/-2.2/day; 7% vs. 2.4+/-3.6/day; 14%; P<0.05). Three months after colostomy/ileostomy closure, the maximum tolerable volume, threshold volume and compliance were decreased after CAA when compared with CPA (55+/-12, 34+/-12, and 3.9+/-0.3 ml/mmHg vs. 85+/-21, 53+/-11 and 6.2 ml/mmHg, respectively; P<0.05). Anal manometry revealed no significant differences in the anal resting and squeeze pressure. One year postoperatively, continence also did not differ significantly between CPA and CAA. Colonic J-pouch reconstruction seems to be superior to the straight coloanal anastomosis, especially during the first postoperative year. In view of the often poor prognosis of the patients, it is the reconstruction of choice after ultra-low resections of the rectum.
Anal Canal↗
Outcome and follow-up of aortic valve replacement with the freestyle stentless bioprosthesis.
BACKGROUND: The aim of this study was to determine the morbidity, mortality, and hemodynamics after implantation of the Freestyle stentless bioprosthesis in the aortic position. METHODS: A total of 280 patients were operated on from June 1993 to July 1999 as part of a multicenter investigation. Factors influencing hospital mortality and long-term survival were assessed by logistic regression and Cox proportional hazards analysis. Patients were evaluated postoperatively at discharge, at 3 to 6 months, and yearly by clinical examination and color flow Doppler echocardiography. RESULTS: Hospital mortality in this group was relatively high (9.6%). Logistic regression analysis showed that cross-clamp time, age, myocardial infarction, diabetes, left ventricular hypertrophy, coronary artery disease, New York Heart Association class III or IV and female gender were the independent predictive factors. According to the Kaplan-Meier method, the 4-year survival for hospital survivors was 94%. In the multivariate Cox proportional hazard analysis, only coronary artery disease proved to be prognostic. During follow-up, 11 patients developed paravalvular leakage due to prosthetic dehiscence at the side of the noncoronary cusp. Performance of the prosthesis as assessed by echocardiography was excellent. Mean gradient decreased significantly between discharge and follow-up at 3 to 6 months. At 1-year follow-up trivial regurgitation was found in 6 patients (3%) and mild regurgitation in 4 (2%). Regurgitation did not increase with time. The effective orifice area increased significantly from discharge to follow-up at 3 to 6 months. CONCLUSIONS: Hospital mortality after implantation of a stentless bioprosthesis was higher compared to conventional prosthesis. A high incidence of prosthesis dehiscence at the proximal suture line was found, which was probably due to technique. Hemodynamic performance up to 3 years showed low transvalvular gradients. There is echocardiographic evidence for reduction of left ventricular hypertrophy and improvement of left ventricular function.
Actuarial Analysis↗
Simulation and analysis of magnetic resonance elastography wave images using coupled harmonic oscillators and Gaussian local frequency estimation.
New methods for simulating and analyzing Magnetic Resonance Elastography (MRE) images are introduced. To simulate a two-dimensional shear wave pattern, the wave equation is solved for a field of coupled harmonic oscillators with spatially varying coupling and damping coefficients in the presence of an external force. The spatial distribution of the coupling and the damping constants are derived from an MR image of the investigated object. To validate the simulation as well as to derive the elasticity modules from experimental MRE images, the wave patterns are analyzed using a Local Frequency Estimation (LFE) algorithm based on Gauss filter functions with variable bandwidths. The algorithms are tested using an Agar gel phantom with spatially varying elasticity constants. Simulated wave patterns and LFE results show a high agreement with experimental data. Furthermore, brain images with estimated elasticities for gray and white matter as well as for exemplary tumor tissue are used to simulate experimental MRE data. The calculations show that already small distributions of pathologically changed brain tissue should be detectable by MRE even within the limit of relatively low shear wave excitation frequency around 0.2 kHz.
Algorithms↗
The Crohn's disease-associated bacterial protein I2 is a novel enteric t cell superantigen.
An aberrant T cell response to enteric bacteria is important in inflammatory bowel disease. However, the identity of relevant microbial antigens is unknown. Here, we report the presence of I2, a Crohn's disease-associated microbial gene, in the murine intestine. The I2 protein induced a proliferative and IL-10 response by CD4(+) T cells from unimmunized mice. The I2 response was dependent on MHC class II-mediated recognition but did not require antigen processing. Selective activation was observed for the TCR-Vbeta5 subpopulation. These findings indicate that the I2 protein is a new class of T cell superantigen and suggest that colonization by the I2 microorganism in susceptible hosts may provide a superantigenic stimulus pertinent to Crohn's disease pathogenesis.
Amino Acid Sequence↗
Panhypopituitarism associated with severe retroperitoneal fibrosis.
A 43-year-old man, with a history of central diabetes insipidus diagnosed 3 years previously, complained about reduced libido. An MRI scan showed a suprasellar lesion just below the supraoptic recess of the third ventricle. A stereotactically guided biopsy revealed fibrous glia, but no other specific tissue and no inflammatory cells. Two months later the patient presented with fatigue and muscular weakness. Tertiary adrenal failure and hypothyroidism were diagnosed by endocrine function tests and therapy with levothyroxine and hydrocortisone was started. Another 2 months later the patient was admitted with giddiness, nausea, peripheral oedema and oliguria. Radiological imaging and an open transperitoneal kidney exploration showed severe fibrosis around both ureters. Histological examination confirmed the diagnosis of idiopathic retroperitoneal fibrosis. Presumably the suprasellar tumour was the first manifestation of retroperitoneal fibrosis. Once the diagnosis 'idiopathic retroperitoneal fibrosis' is confirmed, fibrotic manifestations and complications involving extra-retroperitoneal tissues including the endocrine system, should be sought.
Adult↗
CT angiography of the carotid arteries in trauma to the neck.
OBJECTIVES: serious vascular injuries to the neck may be asymptomatic or masked by other life-threatening conditions. Angiography, the "gold standard" vascular imaging modality, is an invasive procedure. Moreover, it is time-consuming and thus may delay a needed vascular intervention. The results of screening angiography are negative in more than 80% of cases. Therefore other less invasive and faster screening tests, such as the Doppler ultrasound and magnetic resonance angiography, have been tested. This retrospective study was done to evaluate the use of CT angiography (CTA) in suspected vascular injuries of the neck. METHODS: from 1995 to 1998, 16 patients with suspected traumatic carotid artery injury underwent CTA. Twelve of these patients had penetrating injuries and four had blunt injuries to the neck. CTAs were obtained by Elscint Twin Flash Spiral Scanner, while MIP reconstructions were carried out on an Omnipro, Elscint (Indy, Silicon Graphics) work station and interpreted by a radiologist. RESULTS: all the CTAs were diagnostic. Positive findings included one complete tear of the right common carotid artery (confirmed by surgery) due to a penetrating injury and one bilateral internal carotid artery thrombosis after blunt injury to the neck. In addition, three patients with multiple trauma were operated on, due to either proximity only or questionable neurological findings. Surgical exploration confirmed the negative findings seen on CTA. CONCLUSION: CT angiography of the carotid arteries in cervical trauma may be used as an accurate decisive tool for a needed surgical intervention. More studies with larger number of patients and comparison with angiography are needed.
Adolescent↗
[Adaptation of parents to the diagnosis of a chronic disease in their child].
The course and the adaptivity of parental coping with a chronical disease in their child (leukemia, solid tumors, diabetes or epilepsy) was studied during the first three months after diagnosis. 66 parents answered questionnaires to their coping and their quality of life as well as to the perceived quality of life of their children 1-2 weeks and again 8-12 weeks after diagnosis. As coping was stable, the parents' and children's quality of life increased over time. Coping strategies using communication and social support improved the physical well-being of the parents. Family orientation and optimism are helpful for parents and children, too, but rumination decreased emotional well-being of the parents. Psychosocial care for families with a chronically ill child should improve open communication and social orientation in an early stage of the disease and should try to change maladaptive cognitive reactions.
Adaptation, Psychological↗
Reverse transcriptase template switching during reverse transcriptase-polymerase chain reaction: artificial generation of deletions in ribonucleotide reductase mRNA.
Using reverse transcriptase-polymerase chain reaction (RT-PCR), we have recently described a bona fide deletion within the coding sequence of the large subunit of ribonucleotide reductase (R1) mRNA in colon cancer. Consecutive studies have raised questions about the nature of this phenomenon, because the corresponding genomic alteration at the DNA level or an aberrant protein could not be detected. Thus we considered an in vitro artifact during RT-PCR as a possible explanation for this observation. In contrast to reverse transcriptase, Taq DNA polymerase or C. therm DNA polymerase did not generate the aberrant product, suggesting the demand for the template switching activity intrinsic to retroviral reverse transcriptases. In fact, virtually the same deletion was observed in RT-PCR experiments when in vitro transcribed R1 mRNA was used. Considering structural prerequisites for template switching within R1 mRNA, we show that two direct repeats adjacent to a strong stem-loop secondary structure flank the deleted region of 1851 base pairs. Because several mRNAs encoding proteins of clinical and diagnostic importance fulfill these criteria, template switching enhances the potential risk of observing artifacts when interpreting results from RT-PCR studies. As shown in the present example, this may involve the artificial generation and the misinterpretation of PCR fragments amplified from targets relevant to tumor biology or cancer pharmacology. As a possible solution, one-step PCR with C. therm polymerase should be considered. This polymerase eliminates the artificial generation of aberrant mRNA signals observed during cDNA synthesis.
Adenocarcinoma↗
Ocular pANCA antigens are expressed in nonpigmented ciliary body epithelium and are conserved in multiple mammalian species.
PURPOSE: pANCA marker autoantibody is expressed by a subset of patients with anterior uveitis. A recombinantly isolated pANCA monoclonal antibody, Fab 5-3, identifies ocular expression of corresponding pANCA antigens in human ciliary body and retina. In this study, Fab 5-3 was used to explore pANCA antigen expression in ocular tissues of multiple mammalian species and identify the ciliary body cell type expressing the pANCA antigen. METHODS: Ocular tissues were obtained from several mammalian species and evaluated for expression of the pANCA (Fab 5-3) antigen(s) using immunohistochemistry and Western analysis of tissue extracts. Additionally, primary cultures of nonpigmented and pigmented rabbit ciliary body epithelium were analyzed for pANCA expression using immunofluorescence and Western analysis. RESULTS: Ocular pANCA (Fab 5-3) antigen expression was observed by immunohistochemistry only in the cytoplasm of retinal ganglion cells and ciliary body epithelium. Retinal antigen expression was conserved in all species examined. Ciliary body expression was observed in human, rabbit, rat, and mouse, but not in pig or cow. Antigen expression in the rabbit ciliary body was restricted to the nonpigmented layer as defined in primary cultures of nonpigmented and pigmented ciliary body epithelium. Immunoreactive proteins in both the human and rabbit included a 32-33 kDa doublet (histone H1), and novel 80 and 100 kDa proteins. CONCLUSIONS: This study identifies ocular pANCA antigen expression in multiple mammalian species localized to the retinal ganglion cell layer and the non-pigmented ciliary body epithelium. The present study also establishes novel 80 and 100 kDa proteins which may correspond to the cytoplasmic antigens detected in situ and can be further characterized biochemically and immunologically using small animal model systems.
Animals↗
New treatment options in spondyloarthropathies: increasing evidence for significant efficacy of anti-tumor necrosis factor therapy.
Tumor necrosis factor-alpha is a major effector and regulatory cytokine, which seems to have an outstanding position in rheumatic and other inflammatory states. Because TNF-alpha has been detected in the inflamed gut and sacroiliac joints of patients with chronic inflammatory bowel diseases and spondyloarthritides, like ankylosing spondylitis, there was need for studies of the efficacy of the modern biologic anti-TNF agents infliximab and etanercept in these diseases. Infliximab is approved for the treatment of Crohn disease. In addition, there are now also positive data for infliximab in the treatment of ankylosing spondylitis and for etanercept and infliximab in the treatment of psoriatic arthritis.
Antibodies, Monoclonal↗
Entheses and enthesitis: a histopathologic review and relevance to spondyloarthritides.
There are two types of entheses: fibrous, by Sharpey's fibers in membranous bone, and fibrocartilaginous, on endochondral bone, with discontinuous cement lines at the interface between insertion and bone. The connection of hyaline cartilage to subchondral bone is a kind of fibrocartilaginous enthesis. Fibrocartilages are structurally, chemically, and biomechanically intermediate between tendon and cartilage. Enthesitis is not the sole pathologic feature of spondyloarthritides. Synovitis and subchondral bone marrow changes outside the ligamentous insertions, and cartilage proliferation, are important too. In the subentheseal bone marrow and in the synovium, CD8+ T cells play a central role. Imaging of early changes is better achieved by ultrasonography and even better by magnetic resonance imaging than by radiography. No single immunologic target can be identified. The G1 domain of aggrecan is the best candidate, but this does not apply to fibrous entheses. In these complex pathologic conditions, no single abnormality can thus far be designated as a unique hallmark.
Bone and Bones↗
Molecular cloning of a Bacteroides caccae TonB-linked outer membrane protein identified by an inflammatory bowel disease marker antibody.
Commensal enteric bacteria are a required pathogenic factor in inflammatory bowel disease (IBD), but the identity of the pertinent bacterial species is unresolved. Using an IBD-associated pANCA monoclonal antibody, a 100-kDa protein was recently characterized from an IBD clinical isolate of Bacteroides caccae (p2Lc3). In this study, consensus oligonucleotides were designed from 100-kDa peptides and used to identify a single-copy gene from the p2Lc3 genome. Sequence analysis of the genomic clone revealed a 2,844-bp (948 amino acid) open reading frame encoding features typical of the TonB-linked outer membrane protein family. This gene, termed ompW, was detected by Southern analysis only in B. caccae and was absent in other species of Bacteroides and gram-negative coliforms. The closest homologues of OmpW included the outer membrane proteins SusC of Bacteroides thetaiotaomicron and RagA of Porphyromonas gingivalis. Recombinant OmpW protein was immunoreactive with the monoclonal antibody, and serum anti-OmpW immunoglobulin A levels were elevated in a Crohn's disease patient subset. These findings suggest that OmpW may be a target of the IBD-associated immune response and reveal its structural relationship to a bacterial virulence factor of P. gingivalis and periodontal disease.
Amino Acid Sequence↗
Low T cell production of TNFalpha and IFNgamma in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism.
OBJECTIVE: To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon gamma (IFNgamma), interleukin 4 (IL4), tumour necrosis factor alpha (TNFalpha), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls. METHODS: Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and 22 healthy HLA-B27 negative controls) were stimulated with phorbol myristate acetate/ionomycin for six hours, surface stained for CD3 and CD8, intracellularly stained for the cytokines IFNgamma, TNFalpha, IL4, and IL10, and analysed by flow cytometry. TNFalpha production was related to the genotype of the TNFalpha promoter at the -308 and -238 polymorphisms. RESULTS: In peripheral blood the percentage of TNFalpha+ T cells was significantly lower in HLA-B27 positive patients with AS (median 5.1% for CD4+ T cells) than in healthy HLA-B27 negative controls (median 9.5%; p=0.008). Surprisingly, the percentage of TNFalpha+ T cells was also significantly lower in healthy HLA-B27 positive controls (median 7.48%) than in healthy HLA-B27 negative controls (p=0.034). Furthermore, the percentage of IFNgamma+ T cells was lower in patients with AS and in healthy HLA-B27 positive controls than in healthy HLA-B27 negative controls (p=0.005 and p=0.003, respectively). The percentage of IL10+/CD8+ T cells was higher in patients with AS than in both control groups. In HLA-B27 positive subjects, TNF1/2 heterozygosity at -308 (n=6) was associated with a higher percentage of TNFalpha+ T cells than TNF1/1 homozygosity (n=25; median 9.97% v 5.11% for CD4+ T cells; p=0.017). In contrast, in HLA-B27 negative controls (n=18) there was no such genotype/phenotype correlation (median 9.4% v 10.6%). CONCLUSIONS: The lower T cell production of TNFalpha and IFNgamma shown at the single cell level in HLA-B27 positive patients with AS and healthy HLA-B27 positive controls may contribute to the increased susceptibility of HLA-B27 positive subjects to develop AS. Preliminary genotype-phenotype correlations suggest that in HLA-B27 positive subjects TNF2 at -308 or a linked gene results in higher TNFalpha production and, therefore, might be a marker for a protective haplotype.
Adult↗
Low incidence of reactive arthritis in children following a salmonella outbreak.
OBJECTIVES: To assess the incidence of reactive arthritis (ReA) in an outbreak of salmonella infection in a large cohort of children in Germany. METHODS: A few days after the salmonella outbreak all parents of affected children and all paediatricians and general practitioners in the region were provided with detailed information about the possibility of ReA. Six weeks after the outbreak a telephone call was made to all general practitioners and paediatricians to identify patients with ReA. Ten weeks after the outbreak a questionnaire assessing symptoms of ReA was mailed to all parents, and after a period of 4 months paediatricians and general practitioners were contacted again to search for additional unreported cases of ReA. RESULTS: Of the 286 children (age range 11 months to 9 years) with diarrhoea and stool cultures positive for Salmonella enteritidis lysotype 8/7, not a single case of arthritis was reported over the 4 month period. However, six children (2%) had arthralgia of various duration (1 day to 6 weeks) with a single recurrence in one child. The joint pattern was oligoarticular and lower limb joints (knee/ankle) were affected exclusively. CONCLUSION: The incidence of ReA after salmonella infection in children appears to be very low which may be related to differences in the immune response between children and adults.
Arthritis, Reactive↗
Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis.
OBJECTIVE: Reactive arthritis (ReA) triggered by Chlamydia trachomatis or enteric bacteria such as yersinia, salmonella, Campylobacter jejuni, or shigella is an important differential diagnosis in patients presenting with the clinical picture of an undifferentiated oligoarthritis (UOA). This study was undertaken to evaluate the best diagnostic approach. PATIENTS AND METHODS: 52 patients with ReA, defined by arthritis and a symptomatic preceding infection of the gut or the urogenital tract, and 74 patients with possible ReA, defined by oligoarthritis without a preceding symptomatic infection and after exclusion of other diagnoses (UOA), were studied. The following diagnostic tests were applied for the identification of the triggering bacterium: for yersinia induced ReA-stool culture, enzyme immunoassay (EIA), and Widal's agglutination test for detection of antibodies to yersinia; for salmonella or campylobacter induced ReA-stool culture, EIA for the detection of antibodies to salmonella and Campylobacter jejuni; for infections with shigella-stool culture; for infections with Chlamydia trachomatis-culture of the urogenital tract, microimmunofluorescence and immunoperoxidase assay for the detection of antibodies to Chlamydia trachomatis. RESULTS: A causative pathogen was identified in 29/52 (56%) of all patients with ReA. In 17 (52%) of the patients with enteric ReA one of the enteric bacteria was identified: salmonella in 11/33 (33%) and yersinia in 6/33 (18%). Chlamydia trachomatis was the causative pathogen in 12/19 (63%) of the patients with urogenic ReA. In patients with the clinical picture of UOA a specific triggering bacterium was also identified in 35/74 (47%) patients: yersinia in 14/74 (19%), salmonella in 9/74 (12%), and Chlamydia trachomatis in 12/74 (16%). CONCLUSIONS: Chlamydia trachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used.
Adolescent↗
New treatment options in ankylosing spondylitis: a role for anti-TNFalpha therapy.
Anti-TNFalpha treatment seems to be highly effective in AS. The results available indicate that this treatment is at least as effective as in RA. Furthermore, because no other treatments are available for AS--in contrast with RA or psoriatic arthritis--infliximab may even become a first line immunosuppressive treatment in patients with severe active AS. A dose of 5 mg/kg body weight seems to be required and intervals between 6 and 12 weeks seem to be necessary depending on the disease activity. It remains to be seen what the long term effects will be, whether the patients benefit from long term treatment, and whether radiological progression and ankylosis can be stopped. Allergy, lupus-like diseases, and tuberculosis are rare side effects which need to be considered. At first glance, the possible benefits of anti-TNFalpha treatment seem to outweigh these shortcomings, including the high cost.
Anti-Inflammatory Agents, Non-Steroidal↗
Leucocyte response and anti-inflammatory cytokines in community acquired pneumonia.
BACKGROUND: In the host defence of the lung neutrophils (PMN) play a central role. Apart from antimicrobial properties, recent data indicate that PMN also exert anti-inflammatory effects by stimulation and release of cytokine antagonists such as interleukin-1 receptor antagonist (IL-1ra). METHODS: Cytokine release from lipopolysaccharide stimulated whole blood was studied in 18 patients with community acquired pneumonia (CAP) and severe co-morbidities at admission and after 24 hours. Release of IL-1ra, interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNFalpha), soluble TNF receptor type I (sTNF-RI), and IL-8 was determined by ELISA. RESULTS: The mean (SD) leucocyte level at admission was 12.5 (4.1)/nl. There was a significant correlation between the release of anti-inflammatory cytokines such as IL-1ra and sTNF-RI and the leucocyte count at admission and after 24 hours. Additional in vitro experiments showed that co-incubation of peripheral blood mononuclear cells with autologous PMN led to a marked dose dependent increase in IL-1ra and sTNF-RI release. CONCLUSION: These results indicate that PMN may be responsible for the increase in anti-inflammatory cytokines in CAP. Strategies to increase neutrophil counts may exert beneficial effects, not only by augmenting the antimicrobial activity but also by modulating the inflammatory cytokine response.
Adult↗