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The CAST-CAPP axion haloscope, operating at CERN inside the CAST dipole magnet, has searched for axions in the 19.74 µeV to 22.47 µeV mass range. The detection concept follows the Sikivie haloscope principle, where Dark Matter axions convert into photons within a resonator immersed in a magnetic field. The CAST-CAPP resonator is an array of four individual rectangular cavities inserted in a strong dipole magnet, phase-matched to maximize the detection sensitivity. Here we report on the data acquired for 4124 h from 2019 to 2021. Each cavity is equipped with a fast frequency tuning mechanism of 10 MHz/ min between 4.774 GHz and 5.434 GHz. In the present work, we exclude axion-photon couplings for virialized galactic axions down to gaγγ = 8 × 10-14 GeV-1 at the 90% confidence level. The here implemented phase-matching technique also allows for future large-scale upgrades.
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BACKGROUND: Pediatric community-acquired pneumonia (pCAP) often leads to prescription of antibiotics and hospital admission of children. Unfortunately, adherence to diagnosis and treatment guidelines is inconsistent, and misuse of antibiotics may occur. Antimicrobial stewardship interventions, which were started in many hospitals during the last decade, can optimize management of pCAP without negative patient outcomes. OBJECTIVES: The objective of this retrospective analysis was to assess the influence of a newly implemented in-house pediatric antibiotic stewardship (ABS) initiative on guideline adherence and treatment quality. MATERIALS AND METHODS: Retrospective, patients' file-based analysis of the effects of an ABS initiative in a pediatric university hospital from January 2017 until March 2020. ABS initiative included creation of a local pCAP guideline for hospitalized children aged 90 daysâ-â18 years, periodic training and continuous ABS support. RESULTS: A total of 230 patients with pCAP were included (145 before and 85 after intervention). Implementation of the ABS program led to reduction of antibiotics prescription without clear indication from 26â% to 10â% (pâ<â0.05). The inappropriate use of antibiotics decreased from 64â% to 27â% (pâ<â0.05), the rate of incorrect doses declined from 17â% to 10â% (pâ<â0.05) and the mean duration of antibiotic treatment declined from 10 to 7 days (pâ<â0.05). There were no differences between the two groups regarding length of stay, treatment failure or readmissions for respiratory infection. CONCLUSIONS: Pediatric antibiotic stewardship is an appropriate and safe method, and is beneficial to hospitalized patients with pCAP. Application of ABS programs may increase adherence to clinical guidelines and improve appropriate antimicrobial use without negative impact on patient outcomes. Multicenter follow-up studies are needed to clarify long-term effects of ABS programs.
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Gestão de Antimicrobianos , Infecções Comunitárias Adquiridas , Pneumonia , Adolescente , Antibacterianos/uso terapêutico , Criança , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Pneumonia/tratamento farmacológico , Estudos RetrospectivosRESUMO
AIM: We investigated whether the effect of low-dose aspirin on endothelium-dependent vasodilation and arterial stiffness in people with Type 2 diabetes is different from a matched control group. We examined acute and chronic effects, and effects over the 24h dosing interval. METHODS: In an open-label parallel group intervention study, we included 21 participants with Type 2 diabetes and 21 age- and sex-matched controls. Endothelium-dependent vasodilation was assessed as the reactive hyperaemia index (lnRHI) measured by peripheral arterial tonometry (EndoPAT® ). Arterial stiffness was assessed as pulse wave velocity (PWV) measured by applanation tonometry (SphygmoCor® ). Measurements were performed prior to aspirin intake and 1h after aspirin administration (75 mg). Participants were then treated for 6 days, and measurements were repeated at 24 h and 1 h after aspirin intake. RESULTS: Baseline lnRHI did not differ between groups. The controls had an immediate increase in lnRHI after the first aspirin tablet. This was not observed in participants with diabetes (difference between groups; P < 0.05). After 1 week, both groups demonstrated increased lnRHI compared with baseline (P < 0.01). In participants with diabetes, lnRHI was significantly lower 24 h after aspirin administration compared with 1 h after administration (P < 0.05). This difference was not observed in controls (P = 0.84, difference between groups; P = 0.12). The effect on PWV did not differ between groups. CONCLUSION: Aspirin had a reduced immediate effect on endothelium-dependent vasodilation in participants with diabetes. Both groups had improved endothelial function after 1 week of treatment. Further, the effect of aspirin on endothelial function may be declining during a 24 h dosing interval in people with Type 2 diabetes. (Clinical Trial Registry No: 2016-000515-32).
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Aspirina/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Idoso , Aspirina/uso terapêutico , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Endotélio Vascular/fisiologia , Feminino , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Análise de Onda de Pulso , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
BACKGROUND: Cerebral palsy (CP) is the most common motor disability worldwide with an incidence of 2.5 per 1,000 births globally. Health beliefs among caregivers may be major drivers of health-related behaviours and service utilization, but little is known regarding health beliefs around CP in Africa. METHODS: Between July 2013 and September 2015, children with CP were identified in Gaborone, Botswana, and their caregivers were invited to participate in a qualitative study utilizing semistructured in-person one-on-one interviews. Interview questions addressed their understanding of CP, challenges of caring for a handicapped child, and community response to children with CP. RESULTS: Sixty-two caregivers participated in the study. Common themes elicited were variable knowledge about CP, financial and physical burden, lack of therapies and educational resources, and the impact of stigma. Caregivers in Botswana generally subscribed to a biomedical explanation of CP but expressed concerns regarding more stigmatizing folks beliefs expressed in the community. CONCLUSION: Health beliefs regarding CP in Botswana likely have a significant impact on utilization of healthcare resources. Information from this study should inform future educational interventions for caregivers of children with CP.
Assuntos
Cuidadores/psicologia , Paralisia Cerebral/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Botsuana , Paralisia Cerebral/etiologia , Criança , Pré-Escolar , Informação de Saúde ao Consumidor/organização & administração , Efeitos Psicossociais da Doença , Crianças com Deficiência/psicologia , Feminino , Folclore , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Prognóstico , Pesquisa Qualitativa , Estigma Social , Adulto JovemRESUMO
CD101 exerts negative-costimulatory effects in vitro, but its function in vivo remains poorly defined. CD101 is abundantly expressed on lymphoid and myeloid cells in intestinal tissues, but absent from naïve splenic T cells. Here, we assessed the impact of CD101 on the course of inflammatory bowel disease (IBD). Using a T-cell transfer model of chronic colitis, we found that in recipients of naïve T cells from CD101(+/+) donors up to 30% of the recovered lymphocytes expressed CD101, correlating with an increased interleukin (IL)-2-mediated FoxP3 expression. Transfer of CD101(-/-) T cells caused more severe colitis and was associated with an expansion of IL-17-producing T cells and an enhanced expression of IL-2Rα/ß independently of FoxP3. The co-transfer of naïve and regulatory T cells (Treg) protected most effectively from colitis, when both donor and recipient mice expressed CD101. Although the expression of CD101 on T cells was sufficient for Treg-function and the inhibition of T-cell proliferation, sustained IL-10 production required additional CD101 expression by myeloid cells. Finally, in patients with IBD a reduced CD101 expression on peripheral and intestinal monocytes and CD4(+) T cells correlated with enhanced IL-17 production and disease activity. Thus, CD101 deficiency is a novel marker for progressive colitis and potential target for therapeutic intervention.
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Antígenos CD/imunologia , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Interleucina-17/imunologia , Glicoproteínas de Membrana/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Transferência Adotiva , Animais , Antígenos CD/genética , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Colo/imunologia , Colo/patologia , Doença de Crohn/genética , Doença de Crohn/patologia , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Regulação da Expressão Gênica , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-2/genética , Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade beta de Receptor de Interleucina-2/genética , Subunidade beta de Receptor de Interleucina-2/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Ativação Linfocitária , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Knockout , Índice de Gravidade de Doença , Transdução de Sinais , Linfócitos T Reguladores/patologia , Linfócitos T Reguladores/transplante , Células Th17/patologia , Células Th17/transplanteRESUMO
Acyl sugars present in the tomato Solanum lycopersicum 'LA-716' accession confer good levels of resistance to arthropod pests. The objective of the present study was to select F2 plants from the interspecific cross Solanum pennellii 'LA-716' x Solanum lycopersicum 'Redenção' to assess resistance to spider mites (Tetranychus urticae) based on the leaf acyl sugar content and repellence tests. Four genotypes were selected with high leaflet acyl sugar content (RVTA-2010 pl#31, RVTA-2010 pl#75, RVTA-2010 pl#83, and RVTA-2010 pl#94), and an additional three genotypes with low acyl sugar content were also selected (RVTA-2010 pl#33, RVTA-2010 pl#39, and RVTA-2010 pl#73). The results from the in vivo tests used to confirm the selection of plants resistant to mites indicated that the genotypes with high acyl sugars content did not differ from the resistant parent LA-716. The negative correlation between acyl sugar content and the distance run by the mite along the leaflet surface confirmed the association between high and low allelochemical content and resistance. The medium degree of dominance (MDD) was estimated (MDD = -0.83), indicating that the high acyl sugar content was due to incomplete dominance of a recessive allele. A value of 81.85% was found for the broad sense heritability estimate, which suggests that most among-plant variation in the F2 generation is genetically based. Furthermore, 0.69 genes were estimated, which presumably confirms monogenic inheritance. Thus, indirect selection was an efficient method used to obtain industrial tomato plants that are resistant to spider mites.
Assuntos
Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Seleção Genética , Solanum lycopersicum/genética , Solanum lycopersicum/parasitologia , Tetranychidae/fisiologia , Animais , Carboidratos/análise , Distribuição de Qui-Quadrado , Cruzamentos Genéticos , GenótipoRESUMO
The neurochemical environment of nontumorous white matter tissue was investigated in 135 single voxel spectra of "healthy" white matter regions of 43 tumor patients and 129 spectra of 52 healthy subjects. Spectra were acquired with short TE and TR values. With the data of tumor patients, it was examined whether differences were caused by the tumor itself or aggressive tumor therapies as confounding factors. Comparing the spectra of both classes, an excellent differentiation was possible based on the metabolite peak of N-acetylaspartate (P ≈ 0) and myoinositol (P < 0.03). The area under curve of the receiver operating characteristic was calculated as 0.86 and 0.62, respectively. With linear discriminant analysis using combinations of integrals, a prediction was possible, whether a spectrum belonged to the patient or the healthy subject class with an overall accuracy above 80%. The confounding factors could be ruled out as source of the differences. The results show strong evidence for an influence of malignant growth on the biochemical environment of nontumorous white matter tissue. Because of the T(1) weighting, the measured differences between both classes were most likely concentration changes interfered by T(1) effects. The underlying processes will be subject of future studies.
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Ácido Aspártico/análogos & derivados , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Fibras Nervosas Mielinizadas/metabolismo , Adulto , Ácido Aspártico/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrótonsRESUMO
The structural and functional properties of the nicotinic acetylcholine receptor (AChR), the archetype molecule in the superfamily of Cys-looped ligand-gated ion channels, are strongly dependent on the lipids in the vicinal microenvironment. The influence on receptor properties is mainly exerted by the AChR-vicinal ("shell" or "annular") lipids, which occur in the liquid-ordered phase as opposed to the more disordered and "fluid" bulk membrane lipids. Fluorescence studies from our laboratory have identified discrete sites for fatty acids, phospholipids, and cholesterol on the AChR protein, and electron-spin resonance spectroscopy has enabled the establishment of the stoichiometry and selectivity of the shell lipid for the AChR and the disclosure of lipid sites in the AChR transmembrane region. Experimental evidence supports the notion that the interface between the protein moiety and the adjacent lipid shell is the locus of a variety of pharmacologically relevant processes, including the action of steroids and other lipids. I surmise that the outermost ring of M4 helices constitutes the boundary interface, most suitable to convey the signals from the lipid microenvironment to the rest of the transmembrane region, and to the channel inner ring in particular.
Assuntos
Canais Iônicos/química , Canais Iônicos/fisiologia , Lipídeos de Membrana/química , Lipídeos de Membrana/fisiologia , Receptores Nicotínicos/química , Receptores Nicotínicos/fisiologia , Animais , Colesterol/química , Colesterol/fisiologia , Ácidos Graxos/química , Ácidos Graxos/fisiologia , Humanos , Canais Iônicos/efeitos dos fármacos , Fosfolipídeos/química , Fosfolipídeos/fisiologia , Estrutura Secundária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/fisiologia , Receptores Nicotínicos/efeitos dos fármacos , Membranas Sinápticas/química , Membranas Sinápticas/efeitos dos fármacos , Membranas Sinápticas/fisiologiaRESUMO
We have investigated the spectral diffusion and the electron-phonon coupling of B800 bacteriochlorophyll a molecules in the peripheral light-harvesting complex LH2 for three different species of purple bacteria, Rhodobacter sphaeroides, Rhodospirillum molischianum, and Rhodopseudomonas acidophila. We come to the conclusion that B800 binding pockets for Rhodobacter sphaeroides and Rhodopseudomonas acidophila are rather similar with respect to the polarity of the protein environment but that the packaging of the alphabeta-polypeptides seems to be less tight in Rb. sphaeroides with respect to the other two species.
Assuntos
Proteínas de Bactérias/química , Bacterioclorofila A/metabolismo , Biofísica/métodos , Complexos de Proteínas Captadores de Luz/química , Proteobactérias/metabolismo , Rhodobacter/metabolismo , Rodopseudomonas/metabolismo , Rhodospirillaceae/metabolismo , Cristalografia por Raios X/métodos , Difusão , Elétrons , Modelos Moleculares , Conformação Molecular , Peptídeos/química , Ligação Proteica , Proteobactérias/fisiologiaRESUMO
Low-temperature (1.4 K), single-molecule fluorescence-excitation spectra have been recorded for individual reaction center-light-harvesting 1 complexes from Rhodopseudomonas palustris and the PufX(-) strain of Rhodobacter sphaeroides. More than 80% of the complexes from Rb. sphaeroides show only broad absorption bands, whereas nearly all of the complexes from Rps. palustris also have a narrow line at the low-energy end of their spectrum. We describe how the presence of this narrow feature indicates the presence of a gap in the electronic structure of the light-harvesting 1 complex from Rps. palustris, which provides strong support for the physical gap that was previously modeled in its x-ray crystal structure.
Assuntos
Proteínas de Bactérias/química , Complexos de Proteínas Captadores de Luz/química , Rhodobacter sphaeroides/química , Rodopseudomonas/química , Espectrometria de FluorescênciaRESUMO
Epifluorescence, confocal and total internal reflection microscopy are the most widely used techniques for optical single-molecule experiments. Employing these methods, we recorded the emission intensity of the same single molecule as a function of the excitation rate under otherwise identical experimental conditions. Evaluation of these data provides a quantitative comparison of the signal-to-background ratios that can be achieved for the three microscopic techniques.
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We report on the magnetic, thermodynamic, and optical properties of the quasi-one-dimensional quantum antiferromagnets TiOCl and TiOBr, which have been discussed as spin-Peierls compounds. The observed deviations from canonical spin-Peierls behavior, e.g., the existence of two distinct phase transitions, have been attributed previously to strong orbital fluctuations. This can be ruled out by our optical data of the orbital excitations. We show that the frustration of the interchain interactions in the bilayer structure gives rise to incommensurate order with a subsequent lock-in transition to a commensurate dimerized state. In this way, a single driving force, the spin-Peierls mechanism, induces two separate transitions.
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The crystal structure of Ca(2-x)Sr(x)RuO(4) with 0.2 < or = x < or = 1.0 has been studied by diffraction techniques and by high resolution capacitance dilatometry as a function of temperature and magnetic field. Upon cooling in zero magnetic field, the crystal structure and the octahedra shrink along the c direction and elongate in the a and b planes, whereas the opposite occurs upon cooling at high field (x = 0.2 and 0.5). These findings yield evidence for an orbital rearrangement driven by temperature and magnetic field, which accompanies the metamagnetic transition at low temperature. The temperature and magnetic-field dependencies are found to be governed by the same energy scale.
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Using soft-x-ray absorption spectroscopy at the Co L(2,3) and O K edges, we demonstrate that the Co3+ ions with the CoO5 pyramidal coordination in the layered Sr2CoO3Cl compound are unambiguously in the high spin state. Our result questions the reliability of the spin state assignments made so far for the recently synthesized layered cobalt perovskites and calls for a reexamination of the modeling for the complex and fascinating properties of these new materials.
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We report the case of a patient with acquired pure megakaryocytic aplasia. Until today, less than 20 cases of acquired pure megakaryocytic aplasia have been reported and the disease aetiology still seems to be unclear. This report summarizes the published data concerning possible aetiologies, treatment options and outcome of patients with acquired pure megakaryocytic aplasia. Furthermore, this case report presents an example for a possible disease progression.
Assuntos
Megacariócitos/patologia , Trombocitopenia/etiologia , Adulto , Transfusão de Sangue , Doenças da Medula Óssea/etiologia , Doenças da Medula Óssea/patologia , Exame de Medula Óssea , Transplante de Medula Óssea/efeitos adversos , Progressão da Doença , Evolução Fatal , Humanos , Imunossupressores/uso terapêutico , Masculino , Púrpura , Trombocitopenia/terapia , Transplante Homólogo , Resultado do TratamentoRESUMO
High-speed chains or rotating disks are commonly used to cut and process trees during forest harvesting operations. Mechanical failure or fatigue of these tools can lead to a potentially hazardous situation where fragments of chain or sawteeth are thrown through the operator enclosures on forest machines. Therefore, a test device is needed to evaluate the ability of a forest machine cab to resist puncture by thrown objects. This articles details the development of a high-pressure pneumatic launch system that propels sawteeth and chain fragments at velocities in excess of 150 m/s. This article also discusses the performance of the device following the first series of projectile launches.
Assuntos
Acidentes de Trabalho/prevenção & controle , Agricultura Florestal/instrumentação , Equipamentos de Proteção/normas , Gestão da Segurança/métodos , Desenho de Equipamento , Segurança de Equipamentos , Humanos , Masculino , Sistemas Homem-Máquina , Pessoa de Meia-IdadeRESUMO
The source of cells for tissue engineering applications remains a hurdle, predominantly for procedures in which there is insufficient time to harvest a patient's own cells. Animal cells are readily available, but undergo immune rejection. Rejection of animal (i.e., xenogeneic) tissue involves practically every component of the immune system. The initial phase, hyperacute rejection (HAR), involves natural xenoreactive antibodies and the complement system, and leads to endothelial cell lysis and rapid tissue destruction. The cell-surface epitope, galactose-alpha(1,3)-galactose (alphaGal), is presumed to play a key role in HAR. The later stage of immune response (delayed xenograft rejection or DXR), is mediated by immune cells such as monocytes. Carbohydrates are likely also involved in DXR, but their role in this phase of the immune response is less clear. A better understanding of all stages of xenogeneic immune rejection may make it feasible to create cell lines that are immune tolerant. In these studies, we have genetically modified bovine endothelial cells to study the roles of carbohydrates in immune rejection. Our studies suggest that one or more epitopes other than alphaGal may influence complement-mediated lysis. Furthermore, antibodies, as instigators in the complement response, and monocytes appear to recognize different cell surface epitopes.
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Linhagem Celular , Endotélio Vascular/imunologia , Galactosiltransferases/imunologia , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Transplante Heterólogo/imunologia , Animais , Endotélio Vascular/citologia , Endotélio Vascular/transplante , Galactosiltransferases/genética , Humanos , Recém-Nascido , Engenharia Tecidual , Imunologia de TransplantesRESUMO
The objective of this study is to determine if the detection of interleukin-6 (IL-6) in maternal plasma prior to delivery predicts neonatal and/or infectious complications in patients with preterm premature rupture of membranes. Patients with preterm premature rupture of membranes between 24 and 35 weeks' gestation were asked to participate in the study. Maternal blood was obtained prior to delivery. All patients received Ampicillin-sulbactam and steroids. IL-6 concentrations were determined by enzyme-linked immunoadsorbent assay (ELISA) using 50 mL of plasma assayed in duplicate. ELISA sensitivity was 18 pg/mL. Neonatal and infectious complications examined were respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, intra-amniotic infection, presumed neonatal sepsis, neonatal sepsis, and congenital pneumonia. Fifty-seven patients' plasma was analyzed. Thirty-five had positive plasma IL-6 prior to delivery. Twenty-seven patients had at least one neonatal complication with 24 (89%) being positive for IL-6. Of the 30 patients without complications, only 11 (37%) were positive (p = 0.0001, OR 13.8. 95% CI, 2.93-74.7). A subanalysis of patients who received a course of corticosteroids was performed and significance was maintained. Ten of 13 patients (77%) with neonatal complications had positive IL-6 compared with 40% without complications (p Assuntos
Ruptura Prematura de Membranas Fetais/sangue
, Doenças do Prematuro/sangue
, Interleucina-6/sangue
, Complicações Infecciosas na Gravidez/sangue
, Sepse/sangue
, Adulto
, Biomarcadores/sangue
, Feminino
, Humanos
, Recém-Nascido
, Doenças do Prematuro/diagnóstico por imagem
, Valor Preditivo dos Testes
, Gravidez
, Estudos Prospectivos
, Sensibilidade e Especificidade
, Sepse/congênito
, Sepse/diagnóstico
, Ultrassonografia
, Estados Unidos
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In patients with normal immunity, cat scratch disease typically develop a papule at the portal of entry and no other cutaneous features. A 73 year old male patient with a myelodysplastic syndrome developed generalized petechial, papular and, vasculitic skin lesions in association with cat scratch disease. After the diagnosis was established by identifying the causative organism in a lymph node biopsy, the patient was treated with erythromycin for three weeks resulting in progressive clearance of the skin lesions. Apart from the soluble IL-2 receptor, no other serologic inflammatory parameters were elevated. IgG antibodies against Bartonella henselae and Bartonella quintana increased only slightly during acute exacerbation of the disease, but significantly increased some months later. The diagnosis was established by the positive staining of the lymph node biopsy using the Warthin-Starry stain.