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 the location of rRNA that would indicate the presence of metabolically active bacteria. T. whippelii rRNA was most prevalent near the tips of intestinal villi, in the lamina propria, just basal to epithelial cells. Most of the bacterial rRNA signal appeared to be located between cells and did not colocalize with the human intracellular protein vimentin. The location of bacterial rRNA in tissues from patients with Whipple's disease provides evidence that bacteria are growing outside cells and suggests that T. whippelii is not an obligate intracellular pathogen.     

Whipple's arthritis: direct detection of Tropheryma whippelii in synovial fluid and tissue

We describe 2 patients presenting with polyarthritis in whom the synovial fluid (1 patient) or synovial tissue (1 patient) was positive for Tropheryma whippelii, the Whipple's disease-associated bacillus, when examined by polymerase chain reaction (PCR) and DNA sequencing. Histopathologic findings were consistent with articular Whipple's disease in the synovial fluid of 1 patient and the synovial tissue of the other. In both patients, bowel mucosal specimens were negative for Whipple's disease features by histologic and PCR methods. One patient was positive for T whippelii in the peripheral blood. Control synovial fluid specimens from 40 patients with other arthritides, including Lyme arthritis, were negative. Sequencing of a 284-basepair region of the 16S ribosomal RNA gene confirmed that the sequence is closely related to the known T whippelii sequence. Both patients responded to treatment with antibiotics.     

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. Microbiol. Rev. 2001;14:561-583; Medicine (Baltimore) 1997;76:170-184]. Whipple's endocarditis is relatively common in autopsy studies [Can. J. Cardiol. 1996;12:831-834] but has rarely been diagnosed before death. With the advent of molecular diagnostic tools such as the polymerase chain reaction (PCR), Tropheryma whippelii as a cause of culture-negative endocarditis has become increasingly recognized [Clin. Infect. Dis. 2001;33:1309-1316; Ann. Intern. Med. 1999;131:112-116; Infection 2001;29:44-47; Ann. Intern. Med. 2000;132:595]. With this increased recognition has come the realization that Whipple's endocarditis can occur without other common manifestations of Whipple's disease [Ann. Intern. Med. 1999;131:112-116; Infection 2001;29:44-47; Ann. Intern. Med. 2000;132:595]. We report here two cases of Whipple's endocarditis without discrete febrile illness, gastrointestinal manifestations, or arthritic manifestations, diagnosed by PCR of resected valvular material.     

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 specimen was obtained before treatment; the other was obtained 12 months after discontinuation of therapy, at a time of intestinal remission. In both cases, 15 passages of the cultures were completed over 17 months. Bacterial growth was measured by quantitative polymerase chain reaction, which suggested a generation time of 4 days. Staining with YO-PRO nucleic-acid dye showed characteristic rod-shaped bacteria arranged in chains. Fluorescent in situ hybridization with a T. whipplei-specific oligonucleotide probe, a broad-range bacterial probe, and a nonspecific nucleic-acid stain indicated that all visible bacteria were T. whipplei. Scanning electron microscopy and transmission electron microscopy showed both intracellular and extracellular bacteria. This first isolation of T. whipplei from CSF provides clear evidence of viable bacteria in the central nervous system in individuals with WD, even after prolonged antibiotic therapy.     

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 aoritc 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 the 23S rDNA (domain III) sequences. The histological examination of the aortic valve was compatible with Whipple's disease. A duodenal biopsy revealed an infection with Giardia lamblia, but T. whippelii and histological signs of Whipple's disease were not detectable. Received: September 6, 2000 · Revision accepted: December 3, 2000     

Tropheryma whippelii DNA is rare in the intestinal mucosa of patients without other evidence of Whipple disease

BACKGROUND: 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. OBJECTIVE: To assess the presence of T. whippelii in patients undergoing upper endoscopy for a variety of indications. DESIGN: Prospective and routine diagnostic examination of patients. SETTING: Three academic medical centers in California; Minnesota; and Heidelberg, Germany. PATIENTS: 342 patients undergoing endoscopy for evaluation of dyspepsia or possible peptic ulcer (group A, 173 patients), malabsorption (group B, 37 patients), or clinical suspicion of Whipple disease (group C, 132 patients). MEASUREMENTS: Small-intestinal biopsy specimens were tested by polymerase chain reaction for T. whippelii DNA and examined for histopathologic abnormalities. RESULTS: All patients with negative histologic findings also had negative results for T. whippelii DNA. CONCLUSIONS: T. whippelii occurs only rarely in intestinal mucosa that lacks histopathologic evidence of Whipple disease. The human small intestinal mucosa is an unlikely reservoir for this organism.     

Cultivation of Tropheryma whipplei from the synovial fluid in Whipple's arthritis

This report describes a patient who presented with fever, weight loss, diarrhea, and adenopathy. At the time of presentation he had a 28-year history of unusually severe destructive polyarthritis. Duodenal biopsy revealed periodic acid-Schiff-positive macrophages. Polymerase chain reaction studies showed positivity for Tropheryma whipplei in synovial fluid, synovial tissue, and lymph node specimens, and Whipple's disease was diagnosed. T whipplei was successfully cultivated from the synovial fluid by both cell culture and axenic culture. This strain (named ART1) was subcultured and subsequently established and genotyped. Antibiotic treatment was instituted in the patient, after which his symptoms remitted. These findings show for the first time that Whipple's arthritis may be, at least in some cases, a septic arthritis.     

First isolation of Tropheryma whipplei from bronchoalveolar fluid and clinical implications

A patient presented diffuse pulmonary parenchymal micronodules. Tropheryma whipplei was detected in the saliva, a bronchial biopsy and bronchoalveolar fluid. PAS staining, immunohistochemistry and PCR for T. whipplei were negative in the duodenal biopsies. T.?whipplei was isolated from the bronchoalveolar fluid, reinforcing its role as a respiratory pathogen.     

Spontaneous rupture of the esophagus presenting with unilateral proptosis

An unusual case of spontaneous rupture of the esophagus (Boerhaave syndrome) presented initially with only unilateral proptosis secondary to orbital emphysema, without significant chest or abdominal symptoms. The classical signs of chest pain and cardiovascular collapse were absent. The diagnosis was suggested by the presence of mediastinal emphysema on chest roentgenogram. Boerhaave syndrome was seen after a barium swallow, and the patient was taken immediately to surgery and he survived without further complications. The presence of subcutaneous or mediastinal emphysema with or without other classical signs or symptoms should prompt an aggressive search for its origin. Because a decrease in mortality and morbidity occurs with early detection of this syndrome, a brief review of common and uncommon symptoms is presented.     

Erythromelalgia as a presenting manifestation in a patient with essential thrombocythemia complicating renovascular hypertension due to unilateral renal artery stenosis

Erythromelalgia is a kind of cutaneous manifestation, which appears as a thrombotic complication in patients with myeloproliferative disorders such as essential thrombocythemia and polycythemia vera. It is characterized by red, congested distal extremities and a painful burning sensation, and is usually confined to the feet and one or more toes or fingers. A 28-year-old woman visited our hospital due to severe pain in the left thumb, index fingers and right toes. Her right toes and left thumb were erythematous, congested, and warm. She had a high blood pressure level of 190/100 mmHg, and laboratory evaluation revealed marked thrombocytosis. Bone-marrow findings were compatible with essential thrombocythemia. Renal angiography showed obvious stenosis in unilateral right renal artery. Her erythromelalgia immediately disappeared following interventional therapy along with aspirin. A careful history and appropriate evaluation of underlying diseases are important, because erythromelalgia as a microscopic thrombotic complication may be accompanied by vascular stenosis and all the resulting manifestations.     

从脑炎患者脑脊液中检出新生隐球菌

临床上脑膜炎者多由细菌引起,由隐球菌引起的则罕见,近年来随着市场经济的开放搞活和人们生活水平的提高,养殖和玩宠物的人日益增多,由隐球菌引起的感染性疾病在逐年递增,我院１９９５年～１９９７年感染本病的病例数为前２０年６～７倍,特将检出的５例隐球菌性脑膜...     

Antinuclear antibody in pericardial fluid from a patient with primary cardiac lymphoma

Pericarditis may be the initial manifestation of systemic lupus erythematosus. Although it is known that antinuclear antibody can be detected in the serum of patients with a wide variety of diseases, it has been proposed that the detection of antinuclear antibody in serosal fluid is a sensitive and specific test for determining that effusions are due to systemic lupus erythematosus. A case is presented in which antinuclear antibody in high titer was identified in the pericardial fluid of a patient who was found at autopsy to have a primary cardiac lymphoma. The case indicates that antinuclear antibody detected in serosal effusions should not be considered pathognomonic for systemic lupus erythematosus.     

Recurrent infections and bilateral uveitis in a patient with CD8 deficiency

CD8 deficiency is a rare primary immunodeficiency with low or absent peripheral CD8 cells which results from TAP deficiency, Zap 70 deficiency and CD8 alpha gene mutation.We report a 14 year old female who presented with a history of recurrent pneumonia, bronchiectasis, otitis, severe varicella, herpetic lesions of mouth, bilateral uveitis, and cataract formation since the age of 8 years.She had growth failure, a huge spleen and moderate clubbing. In immunologic workup, humoral and phagocytic systems were normal. DTH response to candida, PPD and DT were negative but LTT response to PHA mitogen was normal. HLA typing showed normal class I expression. Flowcytometry of peripheral blood showed CD8: 0 to 2% (absolute count, 0-60 cells/mm3) with increased CD4/CD8 ratio on several occasions.Diagnosis of this patient cannot be HLA class I deficiency (TAP1 or TAP2), because class I expression had been normal. It is possible to be Zap -70 deficiency or CD8 alpha gene mutation. Bilateral uveitis in our patient was a unique presentation which might have resulted because of immune dysregulation in CID.