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cerebral whipple's disease as a cause of reversible dementia.we describe a case of reversible dementia caused by tropheryma whippelii (tw). diagnosis was confirmed by a positive polymerase chain reaction for this pathogen both on serum and cerebrospinal fluid. specific antibiotic therapy resulted in distinct clinical and neuroradiological improvement. control polymerase chain reaction for t. whippelii on serum and cerebrospinal fluid was negative.200515823686
[weight loss, renal insufficiency, aortal stenosis and arthralgias].the 68-year-old male patient complained of weight loss and -- since 15 years -- of arthralgias and had renal insufficiency and an aortic stenosis. despite the lack of intestinal symptoms, m. whipple could be diagnosed, being responsible for his symptoms and clinical signs. under antibiotic and supportive treatment the patient recovered uneventfully.whipple's disease, otherwise known as intestinal lipodystrophy, is a disease with various signs and symptoms. the principal signs are rheumatic compl ...200515772857
deadly carousel or difficult interpretation of new diagnostic tools for whipple's disease: case report and review of the literature.whipple's disease is a rare systemic disorder classically presenting with weight loss, arthralgias, and diarrhea, which was first described in 1907. the causative bacterium tropheryma whipplei, is a fastidious organism not growing on conventional media. before the introduction of polymerase chain reaction (pcr)-based methods, the diagnostic gold standard was histological detection of diastase-resistant periodic acid schiff (pas)-positive macrophages or electron microscopy. as in the present case ...200515750760
molecular evaluation of antibiotic susceptibility of tropheryma whipplei in axenic medium.whipple's disease is a rare multisystem chronic infection, involving the intestinal tract as well as various other organs. tropheryma whipplei is a slow-growing facultative intracellular bacterium that remains poorly understood. in vitro antibiotic susceptibility testing has previously been assessed in cells using a real-time quantitative pcr assay. in this study, we have evaluated the antibiotic susceptibility of three strains of t. whipplei grown in axenic medium using the same assay.200515650004
molecular genetic methods for the diagnosis of fastidious microorganisms.technological innovations in the detection and identification of microorganisms using molecular techniques such as polymerase chain reaction (pcr) have ushered in a new era with respect to diagnostic microbiology. pcr using universal or specific primers followed by identification of amplified product, mainly by sequencing, has enabled the rapid identification of cultured or uncultured bacteria. thus, pcr may allow quick diagnosis of infections caused by fastidious pathogens for which culture cou ...200415638838
metagrowth: a new resource for the building of metabolic hypotheses in microbiology.metagrowth is a new type of knowledge base developed to guide the experimental studies of culture conditions of obligate parasitic bacteria. we have gathered biological evidences giving possible clues to the development of the axenic (i.e. 'cell-free') growth of obligate parasites from various sources including published literature, genomic sequence information, metabolic databases and transporter databases. the database entries are composed of those evidences and specific hypotheses derived fro ...200515608207
progress, problems, and perspectives in diagnosis and treatment of whipple's disease.whipple's disease is a rare chronic infectious disorder first described in 1907 by g.h. whipple. the disorder is caused by the newly identified bacterium tropheryma whipplei and there is evidence that altered immune functions play a role in the manifestation of the disease. the organ systems mostly affected are the joints and the gut, and in the further course often also the heart, lung, brain, and eyes. the intestinal involvement occurs with abdominal pain and diarrhea, which leads to weight lo ...200415598084
[endocarditis caused by tropheryma whippelii].cardiac involvement in whipple's discase is frequent. however, its clinical occurrence without gastrointestinal symptoms is rarely described. whipple's endocarditis occurs ollen in patients wilh native valves, without underlying, disease. it affects frequently more than one valve h, the same patient. its clhlical presentation is generally subacute or chronic. fever and congestive heart failure are fickle. histological findings on the valves suggest the diagnosis, that con be confirmed by pcr tec ...200415532776
whipple's disease.whipple's disease is a rare multisystemic infectious disorder affecting predominantly middle-aged men. clinical manifestations are very variable with a very long, insidious, prediagnostic course. weight loss, chronic diarrhea, arthralgias, and low-grade fever are characteristic features in most patients. although gastrointestinal compromise is very common, atypical clinical forms are being increasingly recognized. although a bacterial cause was strongly suggested for many years, the infectious a ...200415476147
tropheryma whipplei infection of an acellular porcine heart valve bioprosthesis in a patient who did not have intestinal whipple's disease.rare cases of culture-negative infective endocarditis are caused by tropheryma whipplei, the uncommon bacterium of whipple's disease. we evaluated an 80-year-old woman with valvular heart disease but without intestinal whipple's disease. the diagnosis of aortic valve xenograft culture-negative infection with t. whipplei was established by multiple molecular assays and by electron microscopy. first, a pcr with broad-range primers identified the complete 16s ribosomal dna of t. whipplei in biopros ...200415472298
whipple's disease: the first japanese case diagnosed by electron microscopy and polymerase chain reaction.a 52-year-old man presented with diarrhea and 20 kg weight loss in one year. enteroscopy showed diffuse yellow-white shaggy mucosa in the duodenum and jejunum. biopsies of the duodenal mucosa revealed massive infiltration within the lamina propria by foamy macrophages strongly positive for periodic acid-schiff stain. electron microscopy demonstrated numerous bacilli within macrophages of the lamina propria. tropheryma whipplei dna was detected by polymerase chain reaction. the definitive diagnos ...200415335181
whipple disease confined to the central nervous system presenting as a solitary frontal tumor. case report.whipple disease is a rare infection caused by the bacterium tropheryma whippelii. patients usually present with gastrointestinal symptoms or migratory arthralgias. although symptomatic central nervous system (cns) involvement frequently occurs, whipple disease confined to the cns is rare. the authors present the case of a 40-year-old man who was surgically treated for a symptomatic left frontal tumor that had the neuroimaging features of a low-grade glioma (lgg). a histopathological investigatio ...200415309928
cardiac valves in patients with whipple endocarditis: microbiological, molecular, quantitative histologic, and immunohistochemical studies of 5 patients.the pathological features of whipple endocarditis, which is caused by tropheryma whipplei, were histologically evaluated in cardiac valves from 5 patients. we used quantitative image analysis to compare the valvular fibrosis, calcifications, vegetations, inflammation, and vascularization due to whipple endocarditis with those due to non-whipple endocarditis and degenerative valves. we also studied the presence of t. whipplei in valves by immunohistochemical analysis, culture, and polymerase chai ...200415295699
refractory whipple's disease with anaemia: first lessons from capsule endoscopy.whipple's disease is a chronic multisystem disorder caused by infection with the rod-shaped bacterium, tropheryma whippelii. we report the case of a 65-year-old woman with intestinal whipple's disease that had been refractory to monotherapy with a number of antibiotics over a 2-year period. the patient then presented with watery diarrhoea, cachexia (body mass index 18 kg/m (2)) and chronic anaemia (haemoglobin 7.6 g/dl). wireless capsule endoscopy showed that the disease affected the entire smal ...200415243893
whipple's disease with neurological manifestations: case report.whipple's disease (wd) is an uncommon multisystem condition caused by the bacillus tropheryma whipplei. central nervous system involvement is a classical feature of the disease observed in 20 to 40% of the patients. we report the case of a 62 year old man with wd that developed neurological manifestations during its course, and discuss the most usual signs and symptoms focusing on recent diagnostic criteria and novel treatment regimens.200415235743
a rare course of whipple's disease with atypical cardiac manifestation.whipple's disease (wd) is a rare disorder caused by the gram-positive actinomycete tropheryma whippelii (1). an oral route of acquisition is presumed (2). wd is a chronic systemic infection morphologically characterized by foamy pas-positive macrophages. this case report depicts the diagnosis and clinical management of a woman who presented with atypical cardial manifestations of wd and died from severe cardiac impairment by tropheryma whippelii which was confirmed by polymerase chain reaction. ...200415153165
primary diagnosis of whipple's disease in bone marrow.whipple's disease (wd) is a chronic systemic inflammatory disease of infectious origin caused by tropheryma whipplei (tw). abdominal pain and recurrent diarrhea are usually the main symptoms leading to the suspicion of a primary bowel disease. systemic manifestations can mimic hematologic disorders. a 49-year-old man presented with fever, weight loss, long-standing arthralgia, and diarrhea. a duodenal biopsy was unremarkable. bone marrow histology provided no evidence of a malignant hematologica ...200415116337
invasion of the central nervous system by intracellular bacteria.infection of the central nervous system (cns) is a severe and frequently fatal event during the course of many diseases caused by microbes with predominantly intracellular life cycles. examples of these include the facultative intracellular bacteria listeria monocytogenes, mycobacterium tuberculosis, and brucella and salmonella spp. and obligate intracellular microbes of the rickettsiaceae family and tropheryma whipplei. unfortunately, the mechanisms used by intracellular bacterial pathogens to ...200415084504
cerebral whipple's disease diagnosed using pcr: the first case reported from greece.whipple's disease (wd) is a rare multisystemic bacterial infection, with variable clinical manifestations occasionally involving the central nervous system. as the cultivation of the etiologic agent, tropheryma whippelii, is difficult, a laboratory diagnosis is usually based on histological methods. in the last few years, molecular detection of the bacterial 16srrna genes by pcr, with 2 primer sets, has greatly contributed to the ability of clinicians to diagnose this disease. we present a cereb ...200315068393
antibiotic susceptibility of tropheryma whipplei in mrc5 cells.whipple's disease is considered a rare chronic disease with a broad spectrum of clinical manifestations. several antibiotics have been used for the treatment of this disease, and the current reference treatment was determined empirically on the basis of only a few clinical observations. patients should be treated for months, and many relapse after antibiotic withdrawal. we report here the first extensive study on the susceptibilities of three reference strains of tropheryma whipplei to antibioti ...200414982759
infective endocarditis.despite improvements in health care, the incidence of infective endocarditis has not decreased over the past decades. this apparent paradox is explained by a progressive evolution in risk factors; while classic predisposing conditions such as rheumatic heart disease have been all but eradicated, new risk factors for infective endocarditis have emerged. these include intravenous drug use, sclerotic valve disease in elderly patients, use of prosthetic valves, and nosocomial disease. newly identifi ...200414726169
use of genome selected repeated sequences increases the sensitivity of pcr detection of tropheryma whipplei.the availability of the tropheryma whipplei genome offers the putative possibility of choosing logical dna targets. we applied a pcr assay (targeting repeated sequences of t. whipplei) to samples from patients with whipple's disease and to those from members of a control group. when compared to the results seen with regular pcr, the sensitivity of repeat pcr was significantly enhanced (p = 0.02) without alteration of its specificity.200414715790
culture of tropheryma whippelii from the vitreous fluid of a patient presenting with unilateral uveitis. 200314678933
spondylodiscitis as the first manifestation of whipple's disease -a removal worker with chronic low back pain.whipple's disease is a rare systemic infectious disease caused by the actinobacterium tropheryma whipplei. spondylodiscitis is an extremely rare manifestation of the infection and has previously been described in only three case reports. we present a 55-year-old man with persistent lumbago and signs of systemic illness, but without any gastrointestinal symptoms or arthralgia. the signal response in the lumbar spine in magnetic resonance tomography, both native and after intravenous gadolinium ad ...200314677024
whipple disease.whipple disease is a rare disease caused by infection with the bacterium tropheryma whippelii. humans are the only known host for the infection. the signs of systemic infection include gastrointestinal problems, weight loss, and arthritis. signs of central nervous system infection include cognitive changes, supranuclear gaze palsy, altered level of consciousness, and movement disorders. the diagnosis is based on clinical findings as well as microscopic examination of biopsy specimens and, more r ...200314565900
cultivation of tropheryma whipplei from cerebrospinal fluid.whipple disease (wd) is a systemic disorder caused by the bacterium tropheryma whipplei. since the recognition of a bacterial etiology in 1961, many attempts have been made to cultivate this bacterium in vitro. it was eventually isolated, in 2000, from an infected heart valve, in coculture with human fibroblasts. here we report the isolation of 2 new strains of t. whipplei from cerebrospinal fluid (csf) of 2 patients with intestinal wd but no neurological signs or symptoms. one culture-positive ...200312964110
whipple's disease.whipple's disease is an infectious disease caused by a gram-positive bacterium, tropheryma whipplei. the first case was reported in 1907 by gh whipple. its classic symptoms are diarrhea and arthralgias, but symptoms can be various. cardiac or central nervous system involvement, not always associated with digestive symptoms, may also be observed. for a long time, diagnosis has been based on duodenal biopsy, which is positive using periodic acid-schiff staining. however, for patients without diges ...200312959718
genome-based design of a cell-free culture medium for tropheryma whipplei.empirical approaches have guided the development of bacterial cultures. the availability of sequenced genomes now provides opportunities to define culture media for growth of fastidious pathogens with computer modelling of metabolic networks. a key issue is the possibility of growing host-dependent bacteria in cell-free conditions. the sequenced tropheryma whipplei genome was analysed to identify specific metabolic deficiencies. we used this information to design a comprehensive medium that allo ...200312927433
[neurological complications of inflammatory intestinal diseases].a number of neurological symptoms have been described as complications of inflammatory bowel disorders such as coeliac disease, whipple's disease, crohn's disease and ulcerative colitis. the neurology of coeliac disease includes disorders of the central nervous system encompassing cerebellar ataxia, epilepsy, myoclonus, dementia and multifocal leukoencephalopathy. peripheral neuropathies, of axonal and demyelinating types, and myopathies have also been reported. the pathomechanisms are more rela ...200312910446
culture of tropheryma whipplei from human samples: a 3-year experience (1999 to 2002).the culture of tropheryma whipplei, the bacterium responsible for whipple's disease, has been established only recently. our objective is to describe, based on our experience, the culture of t. whipplei in hel cells detected by immunofluorescence staining. over 3 years, we received 18 samples for t. whipplei culture from 15 patients with whipple's disease. ten duodenal biopsy specimens from 10 patients with digestive symptoms were available. five cardiac valves and three blood samples from five ...200312904394
tropheryma whipplei twist: a human pathogenic actinobacteria with a reduced genome.the human pathogen tropheryma whipplei is the only known reduced genome species (<1 mb) within the actinobacteria [high g+c gram-positive bacteria]. we present the sequence of the 927303-bp circular genome of t. whipplei twist strain, encoding 808 predicted protein-coding genes. specific genome features include deficiencies in amino acid metabolisms, the lack of clear thioredoxin and thioredoxin reductase homologs, and a mutation in dna gyrase predicting a resistance to quinolone antibiotics. mo ...200312902375
cloning and sequencing an unknown gene of tropheryma whipplei and development of two lightcycler pcr assays.whipple's disease is a rare infectious illness that can affect any organ system in the body. it is caused by tropheryma whipplei, a gram-positive rod-shaped bacterium with a high g + c content, classified within the actinobacteria. for decades, laboratory detection has been based on microscopy and the periodic acid-schiff (pas) staining of biopsies. recently, pcr has become a useful tool to detect t. whipplei dna in various clinical specimens. however, a positive pcr result does not confirm whip ...200312867093
tropheryma whippelii as a cause of afebrile culture-negative endocarditis: the evolving spectrum of whipple's disease.with the advent of molecular diagnostics culture-negative endocarditis caused by the organism tropheryma whippelii is an increasingly described entity. we describe two patients with afebrile, culture-negative endocarditis caused by t. whippelii who had neither the gastrointestinal nor arthritic manifestations of whipple's disease. whipple's disease is a systemic illness caused by the organism tropheryma whippelii and is typically characterized by diarrhea, weight loss, and arthropathy [clin. mic ...200312860154
whipple's disease: immunospecific and quantitative immunohistochemical study of intestinal biopsy specimens.whipple's disease may be diagnosed by periodic acid-schiff (pas) staining, electron microscopy, or polymerase chain reaction of intestinal biopsy specimens. the aim of this study was to evaluate the diagnostic value of immunohistochemistry and the quantification of infected cells in intestinal whipple's disease. a total of 29 duodenal biopsy specimens from 15 patients with untreated and treated whipple's disease were examined and compared with biopsy specimens from control patients with normal i ...200312827613
arthritis associated with enteric infection.reactive arthritis is classically seen following infection with enteric pathogens such as yersinia, salmonella, campylobacter and shigella. inflammatory arthritis has also been described following other enteric infection with organisms such as clostridium difficile, brucella and giardia. furthermore, arthritis is seen in whipple's disease, caused by the actinomycete tropheryma whippelii. this chapter reviews the current understanding of these conditions (with the exception of brucella, which is ...200312787523
mucosal immune response to tropheryma whipplei.whipple's disease is a rare infectious disease caused by the ubiquitously occurring tropheryma whipplei in predisposed persons. genetic or acquired defects in the mucosal and peripheral immune system become apparent as diminished th1 immune functions with decreased production of il-12 and ifn-gamma accompanied by an increased secretion of il-4. these defects may enable t. whipplei to survive and replicate. the recently established cultivation of the bacterium in hel cells and the isolation from ...200312755367
analysis of conserved non-rrna genes of tropheryma whipplei.the causative agent of whipple's disease, tropheryma whipplei, is a slow-growing bacterium that remains poorly-understood. genetic characterization of this organism has relied heavily upon rrna sequence analysis. pending completion of a complete genome sequencing effort, we have characterized several conserved non-rrna genes from t. whipplei directly from infected tissue using broad-range pcr and a genome-walking strategy. our goals were to evaluate its phylogenetic relationships, and to find wa ...200312747404
molecular evaluation of antibiotic susceptibility: tropheryma whipplei paradigm.tropheryma whipplei, the agent of whipple's disease, grows fastidiously only in cell cultures without plaque production, and only three strains have been passaged. the formation of bacterial clumps in the supernatant precludes enumeration of viable bacteria and mic determination. we evaluated the bacteriostatic effects of fluoroquinolones against two t. whipplei isolates by measuring the inhibition of the dna copy number increase by real-time quantitative pcr. the analysis of the t. whipplei gen ...200312709337
can whipple's disease be transmitted by gastroscopes?to determine whether disinfection protocols currently used for gastroscopes are effective against cultures of tropheryma whipplei.200312683510
marginal and subgingival plaque--a natural habitat of tropheryma whipplei?dna of tropheryma whipplei, the etiologic agent of whipple's disease, has recently been detected in the saliva of healthy subjects. in this pilot study we searched for the habitat of t. whipplei within the oral cavity.200312682813
prevalence of tropheryma whipplei dna in patients with various gastrointestinal diseases and in healthy controls.little is known about the epidemiology of tropheryma whipplei and its prevalence in people without clinical signs of whipple's disease.200312682812
immunodetection of tropheryma whipplei in intestinal tissues from dr. whipple's 1907 patient. 200312672878
whipple arthritis: diagnosis by molecular analysis of synovial fluid--current status of diagnosis and therapy.whipple's disease (wd) is an uncommon polysystem infectious disease. in the present report, we describe a patient who presented with a chronic illness consistent with wd and an avascular necrosis of the right hip joint. wd and its proposed causative bacillus, tropheryma whippelii, was identified by molecular analysis (polymerase chain reaction) in bacterial dna extracted from the synovial fluid. the diagnosis was additionally confirmed by upper gastrointestinal endoscopy and a small bowel biopsy ...200312626799
sequencing and analysis of the genome of the whipple's disease bacterium tropheryma whipplei.whipple's disease is a rare multisystem chronic infection, involving the intestinal tract as well as various other organs. the causative agent, tropheryma whipplei, is a gram-positive bacterium about which little is known. our aim was to investigate the biology of this organism by generating and analysing the complete dna sequence of its genome.200312606174
molecular diagnosis of culture negative infective endocarditis: clinical validation in a group of surgically treated patients.to assess the clinical validity of polymerase chain reaction (pcr) based molecular methods in the microbiological diagnosis of culture negative infective endocarditis in a group of surgically treated patients.200312591825
whipple's disease.whipple's disease, or intestinal lipodystrophy, is a systemic infectious disorder affecting mostly middle-aged white men. patients present with weight loss, arthralgia, diarrhoea, and abdominal pain. the disease is commonly diagnosed by small-bowel biopsy; the appearance of the sample is characterised by inclusions in the lamina propria staining with periodic-acid-schiff, which represent the causative bacteria. tropheryma whipplei has been classified as an actinomycete and has been propagated in ...200312547551
[whipple's disease--a rare cause of neurological symptoms and disorders].whipple's disease is a chronic infection caused by gram-positive bacillus thropheryma whippelii picture with a wide range of clinical manifestation, not only systemic but also neurological. seronegative arthritis or arthralgia may be the only presenting symptom, predating by years gastrointestinal, and also pulmonary, cardiac, renal and neurological manifestations. the diagnosis can be established based on the characteristic histopathological features found in the affected organ (foamy macrophag ...200212523120
[whipple's disease: progress in the diagnosis and review of the literature].whipple's disease is a rare, chronic, multisystemic disease characterized by the presence of fever, diarrhea, weight loss and malabsorption, preceded by arthritis. although whipple's disease almost always includes involvement of the small intestine and the presence of malabsorption, it commonly affects other organs, especially the heart, brain, eyes and joints. whipple's disease greately mimics other diseases and is caused by a cultivation-resistant bacterium. the disease is fatal unless patient ...200212515967
neurologic presentation of whipple disease: report of 12 cases and review of the literature.we report 12 cases of whipple disease in patients with prominent neurologic symptoms, along with 122 cases of whipple disease with nervous system involvement reported in the literature. we analyzed the clinical signs and results of additional examinations in 2 groups: the first group included patients with predominantly but not exclusively neurologic signs, and the second included patients with clinically isolated neurologic presentation of the disease. whipple disease is a multisystemic infecti ...200212441901
diagnosis of wihipple disease by immunohistochemical analysis: a sensitive and specific method for the detection of tropheryma whipplei (the whipple bacillus) in paraffin-embedded tissue.whipple disease is a rare infection characterized clinically by diarrhea, fever, weight loss, arthralgia, malabsorption, and other systemic manifestations. the etiologic agent, tropheryma whipplei, has been cultured only rarely. by using a polyclonal rabbit antibody produced against a cultured strain of t whipplei, tissue sections from 18 patients with whipple disease were studied. specimens from patients with histologic mimics and other infections served as control specimens. immunostaining was ...200212428795
[whipple disease--a rare systemic disease].whipple's disease is a rare, without antibiotic treatment deadly systemic infectious disease caused by the ubiquitary gram positive bacterium tropheryma whipplei. the agent can be demonstrated by light and electron microscopy and by pcr in tissues and body fluids affected. men are affected more often than women. most patients lose weight, have diarrhea, abdominal pain and arthralgias. in 10-40% of cases involvement of the cns, often asymptomatic, is observed. pas-positive macrophages in the lami ...200212422773
[neurological manifestations of whipple disease].whipple disease is an uncommon chronic bacterial infection due to tropheryma whipplei. clinical manifestations are protean (joint pain, fever, weight loss, abdominal pain, lymphadenopathies), and the diagnosis is often delayed. although previously considered a late manifestation of whipple disease, neurological involvement is now frequently the initial clinical manifestation and represents the greatest risk for long-term disability. all patients should be treated and monitored as if they had cen ...200212407308
dysregulated peripheral and mucosal th1/th2 response in whipple's disease.an impaired monocyte function and impaired interferon (ifn)-gamma production has been suggested as a possible pathogenetic factor in whipple's disease (wd) and as a cause for the delayed elimination of tropheryma whipplei in some patients.200212404221
immunohistological detection of tropheryma whipplei (whipple bacillus) in lymph nodes. 200212361821
cerebral whipple's disease with a stroke-like presentation and cerebrovascular pathology.although neurological symptoms are common in whipple's disease, patients rarely have a purely neurological presentation and involvement restricted to the central nervous system is uncommon. a 39 year old woman presented with a meningoencephalitic illness, which responded to penicillin. eleven months later she developed recurrent stroke-like episodes. patchy enhancing meningeal, cortical, and subcortical lesions thought to be vascular in origin developed within nine days of the onset of symptoms. ...200212185176
sicca syndrome associated with tropheryma whipplei intestinal infection.the case of a 61-year-old woman with whipple's disease-associated sicca complex is reported. tropheryma whipplei infection was diagnosed by histological and ultrastructural examination of the jejunal mucosa and sequence analysis of the bacterial 16s ribosomal dna. the role of vitamin a malabsorption in sicca complex secondary to whipple's disease is discussed.200212149393
whipple's disease: a granulomatous masquerader.whipple's disease is a multisystemic infection that affects middle-aged white men. it typically presents with fever, polyarthritis, diarrhea, steatorrhea, and weight loss. many other systems can be involved, however, including the central nervous system, heart, lymphatics, lungs, bone marrow, and skin. recent work has demonstrated the causative organism to be a complex bacteria, tropheryma whipplei. the diagnosis is established most securely by periodic acid-schiff staining of foamy monocyte-mac ...200212092044
detection of tropheryma whipplei dna in feces by pcr using a target capture method.whipple's disease is a rare multisystemic bacterial infection with variable clinical manifestations. for decades, the laboratory diagnosis was based on the demonstration of periodic acid schiff-positive inclusions in macrophages of gastrointestinal biopsies. pcr has improved the diagnosis of whipple's disease due to its increased sensitivity compared to histopathological analysis. to avoid invasive procedures for taking specimens, we have investigated the possibility of detecting tropheryma whip ...200212089263
whipple's disease.whipple's disease is a chronic systemic bacterial infection that predominantly affects middle-aged men. antimicrobial therapy is curative. the causative agent has been identified as tropheryma whippelii. a pcr-based diagnostic test is now available and is particularly useful in patients with early-stage or atypical disease. the test can detect bacterial nucleic acids in tissues and body fluids, including joint fluid. studies using this test found no evidence that t. whippelii may be a common cau ...200212027303
polymerase chain reaction testing for tropheryma whippelii in unexplained isolated cases of arthritis. 200211954000
molecular techniques in whipple's disease.whipple's disease is a systemic infection, caused by the bacterium tropheryma whipplei, with protean clinical manifestations characterized by fever, weight loss, diarrhea, polyarthritis, skin hyperpigmentation and adenopathy. for a long time, due to the inability to culture the causative organism, diagnosis was based on histologic examination of infected tissues, usually duodenal biopsies, which revealed diastase-resistant periodic acid-schiff-positive staining. now, pcr of various tissues or fl ...200111901835
the diagnosis and treatment of whipple's disease.whipple's disease is a rare, chronic, and systemic infectious disease caused by the ubiquitously occurring bacterium tropheryma whippelii. for two reasons, the disease represents a good example for documenting the input of modern molecular-based techniques into pathogenetic, diagnostic, and therapeutic concepts in clinical medicine. first, the unidentified and uncultivable causative organism has been characterized by novel molecular-genetic techniques. second, in contrast to other chronic inflam ...200111892086
quantitative detection of tropheryma whipplei dna by real-time pcr. 200211880458
survival of tropheryma whipplei, the agent of whipple's disease, requires phagosome acidification.tropheryma whipplei was established as the agent of whipple's disease in 2000, but the mechanisms by which it survives within host cells are still unknown. we show here that t. whipplei survives within hela cells by controlling the biogenesis of its phagosome. indeed, t. whipplei colocalized with lysosome-associated membrane protein 1, a membrane marker of late endosomal and lysosomal compartments, but not with cathepsin d, a lysosomal hydrolase. this defect in phagosome maturation is specific t ...200211854238
monoclonal antibodies to immunodominant epitope of tropheryma whipplei.recent isolation of tropheryma whipplei (formerly trophyrema whippelii), the agent of whipple's disease, from the cardiac valve of a patient with whipple's disease endocarditis now allows the detection of reactive epitopes that could be used in a serological assay. in order to propose an enzyme-linked immunosorbent assay (elisa) that uses recombinant t. whipplei antigen, we first determined by western blotting of human, mouse, and rabbit antisera that the common immunodominant epitope is an 84-k ...200211777846
[clinical case of the month. whipple's disease: inaugural psychiatric symptoms].first considered to be a metabolic illness of the gastro-intestinal tract, whipple's disease has progressively been recognized as a systemic bacterial disorder due to tropheryma whippelii and responding to antibiotics. neurological symptoms occur in 10 to 20% of cases either initially or during the disease course. involvement of the central nervous system alone is rare. modern molecular biology methods, i.e. pcr amplification of 16s rrna can be applied to accessible biological fluids and/or tiss ...200111765576
tropheryma whippelii and the (re)emergence of an old disease. 200111764731
primary diagnosis of whipple disease manifesting as lymphadenopathy: use of polymerase chain reaction for detection of tropheryma whippelii.whipple disease is a rare, chronic multisystem disease associated with the recently characterized organism tropheryma whippelii. extraintestinal manifestation involving the central nervous system, heart, and joints occasionally occurs. involvement of the abdominal lymph nodes, especially the mesenteric and periaortic nodes, is not uncommon. however, peripheral lymphadenopathy as the sole clinical manifestation of whipple disease is rare. we describe 2 patients with whipple disease whose initial ...200111764080
detection of a new 16s-23s rrna spacer sequence variant (type 7) of tropheryma whippelii in a patient with prosthetic aortic valve endocarditis. 200111757986
[valvular locations in whipple's disease: report of two cases and review of the literature].whipple's disease is a consequence of an infection due to a bacteria called tropheryma whippelii. endocarditis is frequently described in post mortem studies on this disease but the diagnosis in living patients is uncommon.200111725719
antibodies against recombinant heat shock protein 65 of tropheryma whipplei in patients with and without whipple's disease.tropheryma whipplei is the causative agent of whipple's disease (wd), a chronic, life-threatening infection. laboratory diagnosis is mainly based on pcr and histopathological analysis in duodenal biopsies and other specimens requiring invasive procedures. we have examined the presence of antibodies to recombinant heat shock protein (hsp65) of t. whipplei in patients with whipple's disease as well as in control subjects by western blot and enzyme-linked immunosorbent assay (elisa). a recombinant ...200111714520
concurrent whipple's disease and giardia lamblia infection in a patient presenting with weight loss.whipple's disease is an uncommon systemic disease caused by the recently cultured tropheryma whippelii, classically presenting with gastrointestinal symptoms. we report a patient with weight loss and malabsorption in which whipple's disease and concurrent giardia lamblia infection were diagnosed. moreover, multiple small bowel polyps were present. the relationship between concurrent whipple's disease and giardia lamblia infection is discussed.200111711278
successful treatment of whipple disease diagnosed 36 years after symptom onset.whipple disease is a rare infectious disorder with multiorgan manifestations and a widely varied clinical presentation. involvement of the small intestine with resultant malabsorption is a classic finding, although extraintestinal manifestations such as fever and arthralgias may precede gastrointestinal symptoms by many years. we describe a 63-year-old man in whom whipple disease was diagnosed 22 years after his initial presentation (36 years after symptom onset) with lymphadenopathy, when a bio ...200111605693
tropheryma whipplei circulating in blood monocytes. 200111519522
description of tropheryma whipplei gen. nov., sp. nov., the whipple's disease bacillus.a detailed characterization was performed of the whipple's disease bacillus, strain twist-marseillet, isolated from the cardiac valve of a patient with whipple's disease bacillus endocarditis. this strain was isolated and maintained on human embryonic lung fibroblast monolayers, but could not be cultivated in the absence of living eukaryotic cells. two morphological forms were observed, with differing staining properties; an intracellular form with intact and degenerating bacteria within vacuole ...200111491348
whipple's disease and "tropheryma whippelii".whipple's disease is a rare bacterial infection that may involve any organ system in the body. it occurs primarily in caucasian males older than 40 years. the gastrointestinal tract is the most frequently involved organ, with manifestations such as abdominal pain, malabsorption syndrome with diarrhea, and weight loss. other signs include low-grade fever, lymphadenopathy, skin hyperpigmentation, endocarditis, pleuritis, seronegative arthritis, uveitis, spondylodiscitis, and neurological manifesta ...200111432814
rpob sequence analysis of cultured tropheryma whippelii.until recently no isolate of tropheryma whippelii was available, and therefore genetic studies were limited to those based on pcr amplification of conserved genes. in this study we determined the nucleotide sequence of rpob (encoding the beta-subunit of rna polymerase) from a cultured strain of t. whippelii using degenerate consensus pcr and genome walking. the t. whippelii rpob consists of 3,657 bp with a 50.4% gc content and encodes 1,218 amino acids with a calculated molecular mass of 138 kda ...200111427549
iron loading: a risk factor for whipple's disease?because of impairment of microbial iron acquisition ability, some potential pathogens can cause disease only in iron loaded hosts. tropheryma whippelii, the etiologic agent of whipple's disease, is a possible example. whipple's disease is non-contagious, occurs mainly in middle-aged white males, and displays many, but not all, of the complications of hereditary haemochromatosis. tropheryma whippelii is a gastrointestinal commensal that causes disease in persons who have a th1-th2 imbalance. host ...200111421626
localization of tropheryma whippelii rrna in tissues from patients with whipple's disease.whipple's disease is caused by a cultivation-resistant bacterium, tropheryma whippelii. ultrastructural studies of intestinal biopsy specimens from patients with whipple's disease have shown that intracellular and extracellular bacteria are present, but the preferred site of growth is unknown. tissue sections from 8 patients with whipple's disease and from 19 healthy control subjects were analyzed by use of fluorescence in situ hybridization and laser scanning confocal microscopy, to determine t ...200111262205
a case of aortic valve disease associated with tropheryma whippelii infection in the absence of other signs of whipple's disease.a case of endocarditis caused by tropheryma whippelii is reported. the 69-year-old patient was diagnosed as suffering from severe aortic regurgitation requiring aortic valve replacement, but showed no other symptoms of whipple's disease. t. whippelii was detected in the explanted aortic valve by broad-range pcr amplification of the 16s rdna and subsequent sequence analysis of the product. the etiologic agent was classified as a type 2a sequence variant based on the 16s-23s intergenic spacer and ...200111261759
rapid ribosequencing--an effective diagnostic tool for detecting microbial infection.rapid and reliable identification of microorganisms is a prerequisite for the diagnosis and subsequent treatment of infectious diseases. the identification of pathogenic bacteria is traditionally based on their isolation from clinical samples and propagation on culture medium in the routine laboratory. however, despite clinical signs of infection, culture of the pathogenic agent often fails. this may be due to a low number of microorganisms, prior antibiotic treatment, nonculturable microorganis ...200111261751
bone marrow involvement in whipple's disease: rarely reported, but really rare?infection with tropheryma whippelii, the causative agent of whipple's disease, involves nearly every organ. involvement of bone marrow may be an overlooked area of whipple's disease. we report a case of lymphoma-like whipple's disease with bone marrow involvement together with a brief review of the literature on this topic. despite minimal documentation, bone marrow may be commonly involved in whipple's disease and, although not specific, diastase-resistant periodic acid-schiff (pas)-positive ma ...200111260072
whipple's disease. report of five cases with different clinical features.whipple's disease (wd) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. we present here five cases (four males and one female) ranging in age from 20 to 59 years. all patients had intestinal involvement associated or not with clinical manifestations linked to this organ. vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by tropheryma whippelii, with disappearance of the echocardiog ...200111246283
[whipple's disease. histologic diagnosis after the discovery of tropheryma whippelii].since the microbiological discovery of tropheryma whippelii, whipple's disease has attracted to new attention in clinical medicine. as small intestinal biopsy is the diagnostic procedure, the impact of knowledge about the histopathological features of whipple's disease and its differential diagnosis has increased. pas-positive macrophages in the intestinal mucosa are the diagnostic hallmark, but further subtyping of cells is important. in whipple's disease macrophages with intensely pas-positive ...200111225449
culture and immunological detection of tropheryma whippelii from the duodenum of a patient with whipple disease.culture of tropheryma whippelii has been established only once, in human fibroblast cell lines from a heart valve inoculum. molecular-based diagnostic techniques, although highly sensitive, may be less specific. new diagnostic tools involving isolation of bacteria from contaminated intestinal biopsies and immunohistological detection need to be developed.200111209175
tropheryma whippelii dna is rare in the intestinal mucosa of patients without other evidence of whipple disease.little is known about the pathogenesis of whipple disease, the reservoirs of tropheryma whippelii, and the proportion of persons harboring the bacterium without "classic" intestinal abnormalities.200111177314
whipple's disease and tropheryma whippelii: secrets slowly revealed.whipple's disease was described in 1907 and was designated "intestinal lipodystrophy," despite the detection of bacteria in 1 specimen. this finding was later substantiated by the success of antibiotic therapy, which resulted in dramatic clinical responses, and by use of electron microscopy, which detected monomorphic bacilli in affected tissues. many attempts at culture failed, and these bacteria were characterized as actinomycetes for the first time by means of broad-range 16s rdna amplificati ...200111170954
whipple disease and arthritis.whipple disease is a chronic, multisystem, curable, bacterial infection that usually affects middle-aged men and has a wide range of clinical manifestations. the most common symptoms are weight loss and diarrhea, preceded in three quarters of cases by arthritis for a mean of 6 years. in most patients, periodic acid-schiff staining of proximal small bowel biopsy specimens reveals inclusions within the macrophages, corresponding to bacterial structures. however, patients with various manifestation ...200111148719
endocarditis due to rare and fastidious bacteria.the etiologic diagnosis of infective endocarditis is easily made in the presence of continuous bacteremia with gram-positive cocci. however, the blood culture may contain a bacterium rarely associated with endocarditis, such as lactobacillus spp., klebsiella spp., or nontoxigenic corynebacterium, salmonella, gemella, campylobacter, aeromonas, yersinia, nocardia, pasteurella, listeria, or erysipelothrix spp., that requires further investigation to establish the relationship with endocarditis, or ...200111148009
whipple's disease.whipple's disease is a systemic bacterial infection and the common though not invariable manifestations are diarrhoea, weight loss, abdominal pain, and arthralgia. arthritis or arthralgia may be the only presenting symptom, predating other manifestations by years. virtually all organs in the body may be affected, with protean clinical manifestations. various immunological abnormalities, some of which may be epiphenomena, are described. the causative organism is tropheryma whippelii. the disease ...200011085766
toward a new understanding of whipple's disease.since the first successful antibiotic treatment of whipple's disease in 1952, many breakthroughs have occurred in the diagnosis and treatment of this disease that was once thought fatal. this article provides a historic overview and highlights recent encouraging discoveries regarding this underdiagnosed disease, including the use of polymerase chain reaction techniques and the recent cultivation of the tropheryma whippelii bacterium.200010981027
tropheryma whippelii dna in saliva of patients without whipple's disease.tropheryma whippelii is the causative agent of whipple's disease, a difficult to diagnose systemic illness. amplification of part of its 16s ribosomal rna gene(s) has become a standard diagnostic method because of increased sensitivity as compared to classical histopathological analysis. recently, we demonstrated the presence of t. whippelii dna by pcr in duodenal biopsies and/or gastric juice of a considerable fraction of individuals without clinical signs of whipple's disease. in this follow-u ...200010961527
an uncommon cause of recurrent strokes: tropheryma whippelii endocarditis.cardiac involvement in whipple's disease is not an uncommon phenomenon in autopsies, but its clinical occurrence is often overshadowed by gastrointestinal symptoms. we report a very atypical manifestation of this disorder.200010926970
whipple's disease with isolated central nervous system symptomatology diagnosed by molecular identification of tropheryma whippelii in peripheral blood.we report a new case of whipple's disease (wd) confined to the central nervous system. the patient presented with ataxia, ophthalmoplegia, hypersomnia, hemiparesis and generalized myorhythmia. the diagnosis was confirmed by identification of specific sequences of the causal agent of wd, the actinobacteria tropheryma whippelii (tw), by pcr of dna extracted from peripheral blood. an epidemiological survey of tw in patients with dementia suggests that wd is an uncommon cause of dementia in our popu ...200010846886
cloning and sequencing of a part of the heat shock protein 65 gene (hsp65) of "tropheryma whippelii" and its use for detection of "t. whippelii" in clinical specimens by pcr.using broad-spectrum primers, we have amplified, cloned, and sequenced a 620-bp fragment of the "tropheryma whippelii" heat shock protein 65 gene (hsp65) from the heart valve of a patient with whipple's endocarditis. the deduced amino acid sequence shows high similarity to those from actinobacteria, confirming that "t. whippelii" is indeed a member of this phylum. based on the nucleotide sequence, we have developed a "t. whippelii"-specific seminested pcr. seventeen patients shown to be positive ...200010834984
microbial pathogens with impaired ability to acquire host iron.successful microbial pathogens must be adept in obtaining growth-essential iron from healthy hosts. some potential pathogens, however, are sufficiently impaired in iron acquisition ability so as to be dangerous mainly in hosts with such iron loading conditions as alcoholism, asplenia, hemochromatosis, beta-thalassemia major, or tobacco smoking. the association of six impaired pathogens (capnocytophaga canimorsis, yersinia enterocolitica and y. pseudotuberculosis, vibrio vulnificus, tropheryma wh ...200010831229
organization, structure, and variability of the rrna operon of the whipple's disease bacterium (tropheryma whippelii).whipple's disease is a systemic disorder associated with a cultivation-resistant, poorly characterized actinomycete, tropheryma whippelii. we determined a nearly complete rrna operon sequence of t. whippelii from specimens from 3 patients with whipple's disease, as well as partial operon sequences from 43 patients. variability was observed in the 16s-23s rrna spacer sequences, leading to the description of five distinct sequence types. one specimen contained two spacer sequence types, raising th ...200010809715
cultivation of the bacillus of whipple's disease.whipple's disease is a systemic bacterial infection, but to date no isolate of the bacterium has been established in subculture, and no strain of this bacterium has been available for study.200010699161
dermatomyositis and whipple's disease.a 14-year-old boy presented with a 3-year history of a skin rash typical of juvenile dermatomyositis, and a 2-month history of mild proximal weakness, myalgia, and weight loss. a quadriceps biopsy showed perifascicular fibre atrophy, focal necrosis and regeneration, immunohistochemical labelling for hla-1 on the surface of the fibres, and focal c5-9 deposition in capillaries. macrophages with diastase-resistant, pas-positive cytoplasm were present. ultrastructural studies showed electron dense a ...200010677863
evaluation of a specific nested pcr targeting domain iii of the 23s rrna gene of "tropheryma whippelii" and proposal of a classification system for its molecular variants."tropheryma whippelii"-associated infections are usually confirmed histopathologically by using light microscopy. pcr assays targeting the 16s rrna gene (16s rdna) of "t. whippelii" are increasingly being applied for this purpose. compared to microscopic analysis, pcr seems to be more sensitive, as indicated by the fact that several cases of whipple's disease with negative histopathological findings but positive pcr results have been reported. considering the lack of pathognomonic clinical featu ...200010655352
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