19 results on '"M. Lodde"'
Search Results
2. Barorezeptorakivierungstherapie bei therapierefraktärer Hypertonie: Indikation und Patientenselektion
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N. Mader, H.-G. Predel, Georg Schlieper, J. Börgel, S. Lüders, Manuel Wallbach, S. Parmentier, Dieter Zenker, J. Müller-Ehmsen, Bernhard K. Krämer, Felix Mahfoud, Vedat Schwenger, G. Henning, Marcel Halbach, Hannes Reuter, Martin Hausberg, Oliver Vonend, J. Passauer, M. Lodde, M. van der Giet, Florian P. Limbourg, Joachim Beige, S. Büttner, Michael Koziolek, and Jens Jordan
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03 medical and health sciences ,0302 clinical medicine ,business.industry ,Internal Medicine ,Medicine ,Medical practice ,Electric stimulation therapy ,030212 general & internal medicine ,Medical emergency ,030204 cardiovascular system & hematology ,business ,medicine.disease - Abstract
Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.
- Published
- 2017
3. Computed tomography after nephron-sparing surgery
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Roman Mayr, M. Lodde, Alessio Comai, Armin Pycha, Giampietro Bonatti, and M. Trenti
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medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Contrast Media ,Computed tomography ,Postoperative Complications ,Renal cell carcinoma ,Internal medicine ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Ct findings ,Carcinoma, Renal Cell ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Treatment options ,Nephrons ,General Medicine ,Hepatology ,medicine.disease ,Kidney Neoplasms ,Nephrectomy ,Radiographic Image Enhancement ,Localized disease ,Radiology ,Nephron sparing surgery ,Tomography, X-Ray Computed ,business ,Organ Sparing Treatments - Abstract
The increased use of abdominal cross-sectional imaging has contributed to a greater detection of incidental small renal masses. Treatment options for localized disease renal cell carcinoma include radical nephrectomy or partial nephrectomy (PN), the former being preferred for treatment of early-stage tumors. The most adopted technique for follow-up imaging is contrast-enhanced computed tomography (CT), whose findings can cause uncertainty and unnecessary repetition of examinations. Our purpose is to describe CT findings after PN and to describe evolution in time of such images.
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- 2015
4. A phase IIa, randomized, double-blind, placebo-controlled trial of apilimod mesylate, an interleukin-12/interleukin-23 inhibitor, in patients with rheumatoid arthritis
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Maria J H Boumans, Kris A. Reedquist, Eric W. Jacobson, Joelle Lufkin, Michael O'Meara, Maarten A. de Boer, Alian Bakker, Beatrijs M. Lodde, Paul P. Tak, Danielle M. Gerlag, Arno W R van Kuijk, Sarah Krausz, Clinical Immunology and Rheumatology, Amsterdam institute for Infection and Immunity, Other departments, and Experimental Immunology
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Adult ,Male ,medicine.medical_specialty ,Nausea ,Morpholines ,Immunology ,Placebo-controlled study ,Placebo ,Gastroenterology ,Interleukin-23 ,Arthritis, Rheumatoid ,Rheumatology ,Double-Blind Method ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Pharmacology (medical) ,Adverse effect ,Aged ,business.industry ,Triazines ,Hydrazones ,Middle Aged ,medicine.disease ,Interleukin-12 ,Surgery ,Methotrexate ,Pyrimidines ,Treatment Outcome ,Tolerability ,Rheumatoid arthritis ,Antirheumatic Agents ,Drug Therapy, Combination ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Objective To investigate the safety, tolerability, pharmacokinetics, and efficacy of apilimod mesylate, an oral interleukin-12 (IL-12)/IL-23 inhibitor, in patients with rheumatoid arthritis (RA). Methods We performed a phase IIa, randomized, double-blind, placebo-controlled proof-of-concept study of apilimod, in combination with methotrexate, in 29 patients with active RA (3:1 ratio of apilimod-treated to placebo-treated patients) in 3 stages. Patients received apilimod 100 mg/day or placebo for 4 weeks (stage 1) or 8 weeks (stage 2). In stage 3, patients received apilimod 100 mg twice a day or placebo for 8 weeks, with an optional extension of 4 weeks. Clinical response (Disease Activity Score in 28 joints [DAS28] and American College of Rheumatology [ACR] criteria) was assessed throughout; synovial tissue samples collected at baseline and on day 29 (stages 1 and 2) or day 57 (stage 3) were stained for cellular markers and cytokines for immunohistochemistry analysis. Results While only mild adverse events were observed in stages 1 and 2, in stage 3, all patients experienced headache and/or nausea. Among apilimod-treated patients (100 mg/day), there was a small, but significant, reduction in the DAS28 on day 29 and day 57 compared with baseline. ACR20 response was reached in only 6% of patients on day 29 and 25% of patients on day 57, similar to the percentage of responders in the placebo group. Increasing the dosage (100 mg twice a day) did not improve clinical efficacy. Consistent with clinical results, apilimod did not have an effect on expression of synovial biomarkers. Of importance, we also did not observe an effect of apilimod on synovial IL-12 and IL-23 expression. Conclusion Our results do not support the notion that IL-12/IL-23 inhibition by apilimod is able to induce robust clinical improvement in RA.
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- 2012
5. NOD mouse model for Sjögren's syndrome: lack of longitudinal stability
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Michael Schmidt, Fumi Mineshiba, Marc R. Kok, Changyu Zheng, Bruce J. Baum, Ana P. Cotrim, Beatrijs M. Lodde, Paul P. Tak, Jianghua Wang, and Martin Kriete
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Autoimmune disease ,medicine.medical_specialty ,Saliva ,Salivary gland ,business.industry ,Interleukin ,Nod ,medicine.disease ,Sialadenitis ,Endocrinology ,medicine.anatomical_structure ,Otorhinolaryngology ,Internal medicine ,Diabetes mellitus ,Immunology ,medicine ,business ,General Dentistry ,NOD mice - Abstract
Objectives: The non-obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjogren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno-associated viral (rAAV2) vector transfer of immunomodulatory transgenes to alter the SS-like disease in NOD mice. Data collected over a 2-year period indicated a changing SS phenotype in these mice and this phenomenon was investigated. Methods: 1010 particles rAAV2LacZ/gland were delivered to both submandibular glands (SMGs) of NOD/LtJ mice at 8 weeks (before sialadenitis onset) of age. Salivary flow rates were determined at 8 weeks and time of killing. Blood glucose levels and body weights were measured weekly. After killing, saliva and SMGs were harvested. Analyses of salivary output, inflammatory infiltrates (focus score), SMG cytokine profile, body weight, and diabetes mellitus status were performed. Data from six different experimental studies over 2 years were analyzed and compared. Results: Salivary flow rate, focus score, and SMG cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12(p70), tumor necrosis factor-α and IFNγ showed changes over time. There were no differences for body weight, diabetes mellitus prevalence, or blood glucose level of non-diabetic mice. Conclusion: This retrospective report is the first to describe longitudinal variability in the NOD mouse as a model for SS. We advise other investigators to continuously monitor the SS phenotype parameters and include appropriate controls when studying this disease in NOD mice.
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- 2006
6. Experience with experimental biological treatment and local gene therapy in Sjogren's syndrome: implications for exocrine pathogenesis and treatment
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Bruce J. Baum, Gabor G. Illei, Paul P. Tak, and Beatrijs M. Lodde
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Systemic disease ,medicine.medical_specialty ,Genetic enhancement ,Immunology ,Review ,General Biochemistry, Genetics and Molecular Biology ,Pathogenesis ,stomatognathic system ,Rheumatology ,Immunopathology ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Humans ,Immunologic Factors ,Autoimmune disease ,business.industry ,Gene Transfer Techniques ,Genetic Therapy ,medicine.disease ,eye diseases ,Disease Models, Animal ,stomatognathic diseases ,Sjogren's Syndrome ,Etiology ,Sjogren s ,business - Abstract
Sjogren's syndrome is an autoimmune exocrinopathy, mainly affecting the lacrimal and salivary glands, and resulting in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). The aetiology and pathogenesis are largely unknown, and only palliative treatment is currently available. Data obtained from experimental animal and human studies using biological agents or gene therapeutics can offer insight into the disease process of Sjogren's syndrome. This article reviews the current literature on these approaches and assesses the lessons learnt about the pathogenesis of Sjogren's syndrome.
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- 2006
7. Kinetics of Tempol for Prevention of Xerostomia Following Head and Neck Irradiation in a Mouse Model
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Anastasia L. Sowers, Albert Kingman, Bruce J. Baum, James B. Mitchell, Ana P. Cotrim, Angelo Russo, Beatrijs M. Lodde, and Joseph M. Vitolo
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Cancer Research ,Pathology ,medicine.medical_specialty ,Ratón ,Injections, Subcutaneous ,medicine.medical_treatment ,Radiation-Protective Agents ,Pharmacology ,Xerostomia ,Salivary Glands ,Cyclic N-Oxides ,Mice ,Pharmacokinetics ,Oral administration ,medicine ,Animals ,Head and neck ,Mice, Inbred C3H ,Salivary gland ,business.industry ,Drug Administration Routes ,Head and neck cancer ,Head and neck irradiation ,medicine.disease ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,Models, Animal ,Female ,Spin Labels ,Cranial Irradiation ,Salivation ,business ,Injections, Intraperitoneal - Abstract
Purpose: Radiotherapy is commonly used to treat the majority of patients with head and neck cancers. Salivary glands in the radiation field are dramatically affected by this procedure. The purpose of this study was to examine pharmacokinetic characteristics of the stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) with respect to radioprotection of the salivary glands. Experimental Design: To evaluate the effect of different doses and times of administration, the heads of C3H mice were exposed to a single irradiation dose of 15 Gy, with i.p. tempol injection. To analyze other routes of administration, we injected 275 mg/kg tempol by an i.m., i.v., or s.c. route, 10 minutes before irradiation. We also tested whether oral administration of tempol in a topical form (either in a mouthwash or gel) provided any salivary gland protection. Results: Tempol treatment (137.5 or 275 mg/kg, i.p., 10 minutes before irradiation) significantly reduced irradiation-induced salivary hypofunction (∼50-60%). I.v. or s.c. administration of tempol also showed significant radioprotection, whereas i.m. administration proved to be ineffective. Topical use of tempol, either as a mouthwash or gel, also was radioprotective. Conclusions: Our results strongly suggest that tempol is a promising candidate for clinical application to protect salivary glands in patients undergoing radiotherapy for head and neck cancers.
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- 2005
8. Reversal of Sjogren's-like syndrome in non-obese diabetic mice
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Shohta Kodama, Ildiko Szalayova, Simon D. Tran, Eva Mezey, Denise L. Faustman, Beatrijs M. Lodde, Sharon Key, and Saeed Khalili
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medicine.medical_specialty ,Necrosis ,Concise Report ,Freund's Adjuvant ,Immunology ,Nod ,medicine.disease_cause ,Salivary Glands ,General Biochemistry, Genetics and Molecular Biology ,Autoimmune Diseases ,Diabetes Mellitus, Experimental ,Autoimmunity ,Mice ,Rheumatology ,Mice, Inbred NOD ,Internal medicine ,Diabetes mellitus ,Animals ,Immunology and Allergy ,Medicine ,NOD mice ,Autoimmune disease ,Salivary gland ,business.industry ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Sjogren's Syndrome ,medicine.anatomical_structure ,Endocrinology ,Freund's adjuvant ,Female ,medicine.symptom ,Salivation ,Secretory Rate ,business ,Spleen - Abstract
Background: Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and Sjogren’s-like syndrome. Objective: To test whether a treatment that reverses end-stage diabetes in the NOD mouse would affect their Sjogren’s-like syndrome. Methods: NOD mice have a proteasome defect. Improperly selected naive T cells escape, but can be killed by reintroducing major histocompatibility complex class I self-peptides on matched normal splenocytes. The proteasome defect also impairs nuclear factor kB, a transcription factor in pathogenic memory T cells, increasing their susceptibility to tumour necrosis factor-induced apoptosis stimulated through complete Freund’s adjuvant (CFA). The impact of this two-limb therapy (injections of matched normal splenocytes and CFA) on the autoimmune salivary gland disease of the NOD mice was studied. Results: All NOD mice receiving the above treatment had a complete recovery of salivary flow and were protected from diabetes. Restoration of salivary flow could be the result of a combination of rescue and regeneration of the gland, as confirmed by immunohistochemical analysis. All untreated NOD mice showed a continuous decline in salivary flow, followed by hyperglycaemia and death. Conclusion: This study establishes that a brief intervention in NOD mice with Sjogren’s-like syndrome can reverse salivary gland dysfunction.
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- 2007
9. Evaluating antirheumatic treatments using synovial biopsy: a recommendation for standardisation to be used in clinical trials
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Lars Klareskog, Richard Reece, Stefano Alivernini, Paul P. Tak, Douglas J. Veale, Iain B. McInnes, Ursula Fearon, Carlomaurizio Montecucco, Marleen G H van de Sande, Veronica Codullo, Paul Emery, Beatrijs M. Lodde, Lisa G. M. van Baarsen, Ioana Felea, Danielle M. Gerlag, Costantino Pitzalis, Elsa Vieira-Sousa, Clinical Immunology and Rheumatology, Amsterdam institute for Infection and Immunity, and 01 Internal and external specialisms
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Oncology ,musculoskeletal diseases ,Genetics and Molecular Biology (all) ,medicine.medical_specialty ,Pathology ,Settore MED/16 - REUMATOLOGIA ,Knee Joint ,Biopsy ,Immunology ,Arthritis ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology ,Arthritis, Rheumatoid ,Arthroscopy ,Rheumatology ,Internal medicine ,Synovitis ,Rheumatoid ,Medicine ,Immunology and Allergy ,Humans ,Multicenter Studies as Topic ,Antirheumatic Agents ,Clinical Trials as Topic ,Synovial Membrane ,Treatment Outcome ,Ultrasonography, Interventional ,Biochemistry, Genetics and Molecular Biology (all) ,Rheumatoid arthritis ,Ultrasonography ,synovial biopsy ,medicine.diagnostic_test ,Interventional ,business.industry ,medicine.disease ,Connective tissue disease ,Clinical trial ,medicine.anatomical_structure ,Synovial membrane ,business - Abstract
Inflammation of synovium is one of the hallmarks of rheumatoid arthritis (RA). Analysis of synovial tissue has increased our understanding of RA pathogenesis, aided in identifying potential therapeutic targets and has been used in the response and mechanistic evaluation of antirheumatic treatments. In addition, studies are ongoing, aimed at the identification of diagnostic and prognostic biomarkers in the synovium. This paper outlines the currently used procedures for sampling and processing of synovial tissue, and presents a standardised recommendation to support multicentre translational research.
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- 2011
10. Nutritional status in the healthy longeval population from Sardinia (Italy)
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Roberto Buffa, M. Lodde, M. Cotza, Giovanni Floris, and Elisabetta Marini
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Male ,Mini nutritional assessment ,Aging ,Population ,Longevity ,Medicine (miscellaneous) ,Nutritional Status ,Age Distribution ,Electric Impedance ,Medicine ,Humans ,Sex Distribution ,education ,Geriatric Assessment ,Aged ,Aged, 80 and over ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Malnutrition ,Nutritional status ,Anthropometry ,Sexual dimorphism ,Well nourished ,Nutrition Assessment ,Italy ,Ageing ,Body Composition ,Female ,Geriatrics and Gerontology ,business ,Bioelectrical impedance analysis ,Demography - Abstract
The aim of this study was to evaluate sex- and age-related variations of the nutritional status in the aged population of central Sardinia, a geographical area with a high frequency of long-lived people, particularly men.The sample consisted of 200 subjects over 70 years of age (men: N= 100, age= 81.0 +/- 7.0 years; women: N= 100, age= 81.5 +/- 7.3 years).Orroli (central Sardinia, Italy).Mini nutritional assessment (MNA) and bioelectrical impedance vector analysis (BIVA) were used to evaluate nutritional status and body composition.The indicators revealed a generally good nutritional status. The MNA results (men: 24.6 +/- 2.2; women: 23.4 +/- 2.5) showed that 64.1% of the subjects had a normal nutritional status and only a small proportion (1.2%) could be classified as malnourished. BIVA showed that most subjects (74.2%) were normal, while the prevalence of low body cell mass was 10.7% and that of dehydration 11.2%. According to the MNA, the nutritional status was significantly better in the men. Almost three-quarters of the men (73.1%) were well nourished vs. half of the women (50.6%). A worsening of the nutritional status with age was observed. The proportion of malnourished individuals, as assessed by MNA, increased from 0% to 9.1% from 70-79 to90 years.With respect to their contemporaries from other regions, the elderly of Orroli presented a better nutritional status, a similar worsening with age and generally higher sexual dimorphism.
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- 2010
11. Complications of Incontinent Stomata in Urology
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M. Lodde and A. Pycha
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medicine.medical_specialty ,business.industry ,General surgery ,Stoma care ,Urology ,Medicine ,business - Published
- 2008
12. Use of Intraoperative Methylene Blue Staining (Imbs) in Nerve-Sparing Perineal Radical Prostatectomy
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A. Pycha and M. Lodde
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medicine.medical_specialty ,Nerve sparing ,Blood transfusion ,business.industry ,Prostatectomy ,medicine.medical_treatment ,Urology ,Staining ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Prostate ,medicine ,business ,Methylene blue - Published
- 2008
13. En Bloc Transuretheral Resection of Bladder Tumors
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M. Lodde and A. Pycha
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medicine.medical_specialty ,business.industry ,Medicine ,business ,Resection ,Surgery - Published
- 2008
14. Serum lipid levels in Sjögren's syndrome
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Rose Anne Leakan, P. P. Tak, Marc R. Kok, Beatrijs M. Lodde, Vidya Sankar, Stanley R. Pillemer, Clinical Immunology and Rheumatology, Other departments, and AII - Amsterdam institute for Infection and Immunity
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Male ,medicine.medical_specialty ,Very low-density lipoprotein ,chemistry.chemical_compound ,Rheumatology ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Triglycerides ,Autoimmune disease ,Triglyceride ,Cholesterol ,business.industry ,Lipid Measurement ,Middle Aged ,medicine.disease ,Lipids ,Lipoproteins, LDL ,Endocrinology ,Sjogren's Syndrome ,chemistry ,Rheumatoid arthritis ,Antibodies, Antinuclear ,Immunoglobulin G ,Female ,lipids (amino acids, peptides, and proteins) ,business ,Lipoproteins, HDL ,Lipoprotein - Abstract
Objectives. Altered lipid levels may occur in autoimmune diseases, for example low cholesterol levels have been described in rheumatoid arthritis (RA). Serum lipid profiles in patients with Sjogren's syndrome (SS) have not been investigated. We hypothesized decreased lipid levels in SS patients and an inverse relationship with disease activity. Methods. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides) and additional data regarding disease measures (clinical immunology parameters, focus score from labial salivary gland biopsy, salivary flow and ophthalmological measures) were available for 46 primary SS patients and 12 xerostomic controls. Results. Significant differences between SS patients and controls means (S.D.) were seen for HDL (P^ 0.04) and total cholesterol (P^ 0.02). LDL (P^ 0.12) and triglyceride (P^ 0.08) levels were not different. In SS patients, but not in controls, total cholesterol (P^ 0.003) and HDL cholesterol (P^ 0.003) predicted immunoglobulin G levels. Anti-SSA antibodies were related to a lower total cholesterol (P^ 0.02) and anti-SSB antibodies to a lower HDL cholesterol level (P^ 0.0497). Conclusions. Significant differences were seen in serum lipid levels of primary SS patients and these were associated with serological measures of inflammation. Our results are comparable to earlier findings in RA patients and raise questions related to adverse cardiovascular consequences in SS. Altered lipid levels have been reported in patients with active autoimmune disorders. For example, several groups have reported on various changes in lipid levels in rheumatoid arthritis (RA) patients (1-9). A decreased level of high-density lipoprotein (HDL) cholesterol with inflammation seems to be a consistent finding. Additionally, a higher risk of atherosclerosis and cardiovascular mortality is seen in RA (10). Increased lipid levels have been found in patients with systemic lupus erythematosus (SLE), where disease activity may be related to increases in levels of triglyceride and very low-density lipoprotein (VLDL) cholesterol, while HDL cholesterol was decreased. Inflammatory proteins and autoanti- bodies in SLE are possibly associated with an increased risk of cardiovascular disease (11, 12). Sjogren's syndrome (SS) is a systemic autoimmune disease mainly characterized by ocular and oral dryness (keratoconjuncti- vitis sicca and xerostomia). There is a distinction between primary SS and secondary SS, the latter developing in the presence of other connective tissue diseases, like SLE or RA (13). Sjogren's syndrome occurs predominantly in peri- and post-menopausal women. Detailed investigations of serum lipid profiles or the prevalence of atherosclerosis in patients with SS have yet to be performed. One of the few studies related to this topic has concentrated on the distinction between pseudo-Sjogren's syndrome in patients with hyperlipidaemia and genuine SS using magnetic resonance imaging (MRI) (14). In the present study, we sought to compare serum lipid profiles in patients with primary SS and non-SS xerostomic patients. We hypothesized that serum lipid levels in SS patients would be lower than those in xerostomic controls. Additionally, we investigated the relationship between serum lipid levels and measures of inflammatory disease activity in patients with SS. Based on reports for other autoimmune diseases, we postulated an inverse relationship for such measures with lipid levels.
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- 2006
15. Adult heart block is associated with disease activity in primary Sjögren's syndrome
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P. P. Tak, Beatrijs M. Lodde, Vidya Sankar, Marc R. Kok, Stanley R. Pillemer, Rose Anne Leakan, Clinical Immunology and Rheumatology, Other departments, and AII - Amsterdam institute for Infection and Immunity
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Male ,medicine.medical_specialty ,Pathology ,Systemic disease ,Heart disease ,Heart block ,Immunology ,Gastroenterology ,Electrocardiography ,stomatognathic system ,Rheumatology ,Internal medicine ,Immunology and Allergy ,Medicine ,Humans ,PR interval ,Aged ,Autoimmune disease ,medicine.diagnostic_test ,business.industry ,Autoantibody ,General Medicine ,Middle Aged ,medicine.disease ,Atrioventricular node ,stomatognathic diseases ,medicine.anatomical_structure ,Heart Block ,Sjogren's Syndrome ,Immunoglobulin M ,Antibodies, Anticardiolipin ,Antibodies, Antinuclear ,Immunoglobulin G ,Atrioventricular Node ,Female ,business - Abstract
Objectives: Congenital heart block occurring in the foetus and neonate may be associated with maternal anti-SS-A/anti-SS-B autoantibodies (anti-SSA/anti-SSB). The adult atrioventricular node is generally thought to be resistant to the damaging effects of anti-SSA/anti-SSB. However, case reports suggest that heart block developing in adult Sjogren's syndrome (SS) patients may be associated with these autoantibodies. Therefore, we investigated the relationship between serum antibodies and heart block in adult SS patients. Methods: We abstracted data from clinic patient records. Diagnosis of primary SS was based on American European classification criteria. Electrocardiograms (EKGs), laboratory immunology parameters, lipid profiles, and focus scores from labial salivary gland biopsies were available for 51 SS patients. Fifteen patients had follow-up EKGs. PR interval >= 200 ms was considered to be first-degree heart block. Results: Five patients showed prolonged PR intervals; the presence of heart block was not related to the presence of anti-SSA antibodies. However, significant differences between patients with prolonged and normal PR intervals were seen for mean focus scores (p
- Published
- 2005
16. Effect of human vasoactive intestinal peptide gene transfer in a murine model of Sjogren's syndrome
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Paul P. Tak, Jianghua Wang, Ana P. Cotrim, Bruce J. Baum, Sandra Afione, Beatrijs M. Lodde, Fumi Mineshiba, Clinical Immunology and Rheumatology, Other departments, and AII - Amsterdam institute for Infection and Immunity
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medicine.medical_specialty ,Saliva ,Immunology ,Vasoactive intestinal peptide ,Genetic Vectors ,Submandibular Gland ,Gene Expression ,Apoptosis ,Nod ,General Biochemistry, Genetics and Molecular Biology ,Antibodies ,Adenoviridae ,Pathogenesis ,Mice ,stomatognathic system ,Rheumatology ,Mice, Inbred NOD ,Transduction, Genetic ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Transgenes ,business.industry ,Interleukin ,Epithelial Cells ,Genetic Therapy ,medicine.disease ,Submandibular gland ,Sialadenitis ,Extended Report ,Interleukin 10 ,Endocrinology ,medicine.anatomical_structure ,Sjogren's Syndrome ,Lac Operon ,Models, Animal ,Cytokines ,Female ,business ,Genetic Engineering ,Vasoactive Intestinal Peptide - Abstract
Background: Sjogren’s syndrome (SS), an autoimmune exocrinopathy mainly affecting lachrymal and salivary glands, results in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). The aetiology and pathogenesis are largely unknown; currently, only palliative treatment is available. Objective: To determine whether gene transfer of vasoactive intestinal peptide (VIP), based on its immunomodulatory properties, might be useful in the management of SS. Methods: A recombinant serotype 2 adeno-associated virus encoding the human VIP transgene (rAAV2hVIP) was constructed and its efficacy tested in the female non-obese diabetic (NOD) mouse model for SS after retrograde instillation in submandibular glands (SMGs). 10 10 particles/gland of rAAV2hVIP or rAAV2LacZ (encoding β-galactosidase; control vector) were administered at 8 weeks of age (before sialadenitis onset). Salivary flow rates were determined before vector delivery and at time of death (16 weeks). After death, saliva, serum, and SMGs were harvested. Salivary output, inflammatory infiltrates (focus scores), VIP protein expression, cytokine profile, and serum anti-VIP antibodies were analysed. Results: rAAV2hVIP significantly improved the salivary flow, increased SMG and serum expression of VIP, and reduced SMG cytokines interleukin (IL) 2, IL10, IL12 (p70), and tumour necrosis factor α, and serum RANTES, compared with the control vector. No difference in focus scores or apoptotic rates was found; neutralising antibodies were not detected. Conclusions: Local delivery of rAAV2hVIP can have disease modifying and immunosuppressive effects in SMGs of the NOD mouse model of SS. The new strategy of employing VIP prophylactically may be useful for both understanding and managing the salivary component of SS.
- Published
- 2005
17. Re: Traditional cardiovascular risk factors in primary Sjogren's syndrome: role of dyslipidaemia
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Beatrijs M. Lodde, Stanley R. Pillemer, Vidya Sankar, Marc R. Kok, Rose Anne Leakan, PP Tak, Clinical Immunology and Rheumatology, Other departments, and Amsterdam institute for Infection and Immunity
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Oncology ,education.field_of_study ,medicine.medical_specialty ,business.industry ,Population ,Autoantibody ,Disease ,medicine.disease ,Rheumatology ,Clinical trial ,Internal medicine ,medicine ,Biomarker (medicine) ,Pharmacology (medical) ,education ,Vasculitis ,business ,Dyslipidemia - Abstract
SIR, we would like to thank Gerli et al. [1] for their reply and the post hoc analysis of their recent Sjogren’s syndrome (SS) study [2] performed. This analysis confirmed our findings [3] in relation to the presence of anti-SSA/B autoantibodies and lower total and HDL cholesterol levels. In addition, Gerli et al.’s study showed anti-SSA antibodies, but not lipid levels, to be an independent predictor of mean carotid arterial thickening [2]. As referenced in our article, in RA and SLE several possible factors, including autoantibodies, can lead through vascular damage to a dysfunctional vasculature more susceptible to traditional cardiovascular risk factors, such as cholesterol levels, than in general. In addition, decreased lipid levels tended to predict cardiovascular morbidity and mortality in RA [4]. An association between intima-media thickening and altered lipid levels in SS patients could perhaps, as Gerli and co-authors had suggested, be detected in larger population-based studies with longer follow-up. Gerli et al. believe that the presence of anti-SSA/B autoantibodies is better for disease diagnosis than as a reflection of disease activity. As they indicate, these autoantibodies are thought to be a marker of autoimmune dysregulation characterizing an SS patient’s subset with more severe disease [5, 6]. Indeed, anti-SSA autoantibodies are detected in virtually all SS patients with coexistent vasculitis and in some of these patients it may be the only detectable antibody [7]. Again, this vasculitis can subsequently result in cardiovascular morbidity [8]. Moreover, anti-SSB autoantibody proved to be a highly significant marker of organ involvement in a large cohort of primary SS patients [5]. Interestingly, during an SS outcome measures workshop, Soloman et al. showed in a meta-analysis identifying predictive biomarkers in SS clinical trials that anti-SSB autoantibody may be a promising biomarker, in addition to IgG levels [9]. We agree immune-mediated mechanisms can play a role, but the relative contribution of each of the mechanisms needs to be further elucidated. Precocious atherosclerosis, dyslipidemia and autoimmune dysregulation could all be involved in a potential atherosclerotic risk and subsequently cardiovascular events. Gerli et al.’s and our studies provide the rationale for further research. B. M. LODDE, V. SANKAR, M. R. KOK, R. A. LEAKAN, P. P. TAK, S. R. PILLEMER Gene Therapy and Therapeutics Branch/National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA and Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, The Netherlands Accepted 8 September 2006 Correspondence to: Dr Beatrijs M. Lodde, GTTB/NIDCR, National Institutes of Health, 10 Center Drive, Room 1N114, MSC 1190, Bethesda, MD 20892-1190, USA. E-mail: blodde@mail.nih.gov
- Published
- 2006
18. 1122. Transgenic Vasoactive Intestinal Peptide Shows Local Disease Modifying Effects in a Murine Model of Sjögren's Syndrome
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Sandra Afione, Ana P. Cotrim, Paul P. Tak, Bruce J. Baum, Beatrijs M. Lodde, Fumi Mineshiba, and Jianghua Wang
- Subjects
Pharmacology ,medicine.medical_specialty ,Saliva ,biology ,business.industry ,Vasoactive intestinal peptide ,Alpha (ethology) ,Nod ,medicine.disease ,Sialadenitis ,Virus ,Pathogenesis ,Endocrinology ,stomatognathic system ,Internal medicine ,Drug Discovery ,Immunology ,Genetics ,medicine ,biology.protein ,Molecular Medicine ,Antibody ,business ,Molecular Biology - Abstract
Top of pageAbstract Objective: Sj|[ouml]|gren's syndrome (SS), an autoimmune exocrinopathy mainly affecting lacrimal and salivary glands, results in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). The etiology and pathogenesis are largely unknown; currently, only palliative treatment is available. Gene transfer of vasoactive intestinal peptide (VIP), based on its immunomodulatory properties, potentially may be useful in management of SS. Methods: A serotype 2 recombinant adeno-associated virus encoding the human VIP transgene (rAAV2hVIP) was constructed and its efficacy tested in the female non-obese diabetic (NOD) mouse model for SS following retrograde instillation in submandibular glands (SMGs). 1010 particles/gland of rAAV2hVIP or rAAV2LacZ (encoding |[szlig]|-galactosidase; control vector) were administered at 8 weeks of age (before sialadenitis onset). Salivary flow rates were determined before vector delivery and at time of sacrifice (16 weeks of age). After sacrifice, saliva, serum and SMGs were harvested. Analysis of salivary output, inflammatory infiltrates (focus scores), VIP protein expression, cytokine profile in gland extracts, and serum anti-VIP antibodies was performed. Results: rAAV2hVIP led to significantly improved salivary flow, increased SMG expression of VIP, and reduction of SMG cytokines IL-2, IL-10, IL-12(p70) and TNF-|[alpha]|, and serum RANTES, compared to control vector. There was no difference in focus scores between groups and neutralizing antibodies were not detected. Conclusion: This study shows that local delivery of rAAV2hVIP can have disease-modifying effects in SMGs of the NOD mouse model of SS. This is the first report employing VIP as a potential treatment for SS. This strategy may be useful for both understanding and managing the salivary component of SS.
- Published
- 2005
19. Use of immunocytology to predict bladder cancer presence in patients with asymptomatic hematuria
- Author
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Bernd J. Schmitz-Dräger, C. Mian, L.A. Tirsar, Christian Schwentner, Shahrokh F. Shariat, Paul J. Christos, M. Lodde, Joerg Hennenlotter, Eugene K. Cha, and Madhu Mazumdar
- Subjects
Gynecology ,Cancer Research ,medicine.medical_specialty ,Bladder cancer ,medicine.diagnostic_test ,business.industry ,Cellular biomarkers ,Urology ,Cystoscopy ,medicine.disease ,Asymptomatic ,Oncology ,Upper tract ,Cytology ,medicine ,In patient ,Smoking status ,medicine.symptom ,business - Abstract
242 Background: The uCyt immunocytology assay detects cellular biomarkers for bladder cancer (BCa) in exfoliated urothelial cells. We assessed the performance of uCy for detecting BCa in patients undergoing initial evaluation for asymptomatic hematuria. Methods: Data from 1,182 subjects without a history of BCa undergoing evaluation for hematuria were collected at three centers: EuromedClinic/Urologie24, University of Tübingen, and Central Hospital of Bolzano. All subjects underwent standard workup (i.e., voided cytology, upper tract imaging, and cystoscopy) and immunocytology. Results: Overall, 245 subjects had BCa (20.7%). The sensitivity/specificity/negative predictive value for uCyt and cytology were 82.4%/86.6%/95.0% and 46.5%/94.9%/87.2%, respectively. uCyt (OR 18.3, p Conclusions: uCyt is a strong, independent predictor of BCa in patients with hematuria; it outperforms cytology. uCyt may help with patient counseling, quality of care optimization (referral prioritization), and possibly sparing unnecessary hematuria workup in patients at extremely low risk of BCa. [Table: see text] No significant financial relationships to disclose.
- Published
- 2011
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