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J Reichenbach

Publications and source records attributed to J Reichenbach.

At least 19 recordsLinked to original sources
PubMed2006

Impaired interferon-gamma production in response to live bacteria and Toll-like receptor agonists in patients with ataxia telangiectasia.

Ataxia telangiectasia (AT) is a pleiotropic autosomal recessive neurodegenerative disorder with associated immunodeficiency and cancer predisposition, caused by mutational inactivation of the ATM gene. Early death usually results from lymphoreticular malignancy or recurrent, chronic respiratory infections. Immune deficiency of AT patients is heterogeneous and involves both humoral and cellular responses. Reports on the number and integrity of immunocompetent cells in AT are conflicting. In the early phase of infection, the interleukin (IL)-12/interferon (IFN)-gamma axis plays a crucial role in first-line defence against pathogens. In a whole blood assay we studied the IL-12/IFN-gamma axis in the immune response of AT cells to the Toll-like receptor agonists lipopolysaccharide and heat-killed Staphylococcus aureus, as well as whole live M. bovis bacille Calmette-Guérin (BCG). The function of AT antigen-presenting cells was normal in terms of IL-12 production, while IFN-gamma production by T and natural killer (NK) cells was severely impaired, even in the presence of adequate co-stimulation by exogenous IL-12.

Adolescent↗
PubMed2006

Effectiveness of budesonide nebulising suspension compared to disodium cromoglycate in early childhood asthma.

OBJECTIVE: The optimal treatment for early childhood asthma remains controversial. Budesonide (BUD) has shown superiority over placebo in infants, and over disodium cromoglycate (DSCG) in children aged > 2 years. The aim of this double-blind, randomised, parallel-group study was to compare the effectiveness of nebulised BUD and DSCG in asthmatic children aged < 36 months. RESEARCH DESIGN AND METHODS: 82 infants (mean age 18.0 months [range, 11.6-31.2 months]) with suspected asthma (three exacerbations of dyspnoea and wheezing during the past 12 months, with one or more exacerbations in the past 3 months) were treated for 3 months with nebulised BUD (Pulmicort Respules) 0.5 mg/2 mL bid or DSCG 20 mg/2 mL tid. Follow-up was at 6 months. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with BUD had a lower exacerbation rate than DSCG-treated patients after 3 months of treatment (5.4% vs. 31.7%; p = 0.003) and towards the end of follow-up (30% vs. 49%; p = 0.062). During treatment, days without cough were 80% and 65% for BUD and DSCG, respectively (p = 0.014), and nights without cough were 89% and 78%, respectively (p = 0.016). Side-effects were mild and of similar frequency in both groups. CONCLUSIONS: Inhaled nebulised BUD was well tolerated and more effective than nebulised DSCG in reducing the incidence of asthma exacerbations and days with symptoms. These beneficial effects of BUD were maintained throughout the 6-month follow-up.

Anti-Asthmatic Agents↗
PubMed2005

Growth factor deficiency in patients with ataxia telangiectasia.

One prominent feature of patients with the autosomal recessive disease ataxia telangiectasia (AT) is somatic growth retardation. Due to their essential roles in development we examined levels of insulin-like growth factor-I (IGF-I) as well as its main binding protein (IGFBP-3) in a group of AT patients. Growth status of 19 patients was assessed by body mass index (BMI) and nutritional protocols. As suspected, BMI was low in AT patients despite adequate nutrition. Serum levels of IGF-I were found to be below the 3rd percentile in 9 (56%) out of 16 patients and of IGFBP-3 in 13 (81%) out of 16 patients. Our observations demonstrate that IGF-I and IGFBP-3 levels reflect the impaired growth status in patients with AT.

Adolescent↗
PubMed2003

Safety and tolerability of methacholine challenge in infants with recurrent wheeze.

Bronchial hyperreactivity (BHR) is a key feature of asthma, but measurement can usually not be achieved in infants with standard lung function tests. We investigated the safety and tolerability of methacholine challenge in infants with recurrent wheezing episodes. 78 methacholine challenges in 51 sedated infants aged 12-36 months with recurrent wheezing episodes were performed. Methacholine challenge was stopped when clinical signs (coughing, wheezing, or cyanosis) or a drop of oxygen saturation (SPO2) of at least 5% or a drop of transcutaneous oxygen tension (PtcO2) of at least 0.8 kPa or an increase of resistance (RrsSO), of 50% by single occlusion technique were observed. Prior to methacholine challenge, all children were symptom-free with a mean SPO2 of 97.4% (SD 1.80%). In 48 cases (61.5%), no clinical sign was observed, 17 (21.8%) coughed, and 13 (16.7%) wheezed. A mean reduction of SPO2 of 5.0% (SD 3.89%) for the entire population was observed. In 15 of 78 cases, a decrease of SPO2 <90% occurred. This SPO2 drop was short-lasting and resolved spontaneously or after bronchodilator inhalation. Infants whose SPO2 dropped <90% showed a greater increase of RrsSO compared to infants who did not drop <90% (133% vs. 65% RrsSO increase, p<0.001). Methacholine challenge, using a combination of clinical observation, monitoring of SPO2 and PtcO2, and airway resistance using the single-occlusion technique, is a safe and tolerable tool to measure the BHR in infants with recurrent wheezing episodes.

Airway Resistance↗
PubMed2002

Deficiencies in CD4+ and CD8+ T cell subsets in ataxia telangiectasia.

Chronic sinopulmonary infections that are associated with immunodeficiency are one of the leading causes of death in the multi-systemic disease ataxia telangiectasia (AT). Immunological investigations of AT patients revealed a broad spectrum of defects in the humoral and the cellular immune system. Based on their important role in host defence the aim of our study was an extensive analysis of cell distribution and function of CD4+ and CD8+ T lymphocytes and NK cells. We found that naive (CD45RA+) CD4+ lymphocytes, as well as CD8+/CD45RA+ lymphocytes, are decreased, whereas NK cells (CD3-/CD16+CD56+) are significantly elevated in AT patients. In our culture system proliferation and cytokine production was normal in purified memory (CD45RO+) lymphocytes after stimulation with phorbol-12,13-dibutyrate (PBu2) and after PHA activation, indicating that differences in proliferation and cytokine production are due solely to reduced numbers of CD45RA+ lymphocytes. However, activation, and especially intracellular interferon production of AT lymphocytes, seem to follow different kinetics compared to controls. In contrast to polyclonal activation, stimulation via the T cell receptor results consistently in a reduced immune response. Taken together, our results suggest that deficiency of immunocompetent cells and an intrinsic immune activation defect are responsible for the immunodeficiency in AT.

Adolescent↗
PubMed2001

Interleukin-12 receptor beta1 deficiency in a patient with abdominal tuberculosis.

Two siblings with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency but different clinical phenotypes were studied. Both are homozygous for an IL12RB1 missense mutation that prevents receptor expression and abolishes cellular responses to IL-12. Transfection of the patients' T cells with wild-type IL12RB1 restored IL-12Rbeta1 expression and function. One patient had the expected phenotype of disseminated bacille Calmette-Guérin (BCG) infection in early childhood, whereas the other did not develop BCG infection, despite 3 inoculations with live BCG. Abdominal tuberculosis was diagnosed in this second patient at age 18 years. To date, neither of them has had clinical disease caused by environmental mycobacteria. These observations show unexpected interfamilial and intrafamilial heterogeneity of the clinical phenotype associated with IL-12Rbeta1 deficiency. The patients may be resistant to BCG but remain vulnerable to Mycobacterium tuberculosis. A diagnosis of IL-12Rbeta1 deficiency should therefore be considered in selected patients with severe tuberculosis, despite their resistance to BCG and a lack of atypical mycobacteriosis.

Abdomen↗
PubMed2001

Mycobacterial diseases in primary immunodeficiencies.

Primary immunodeficiency diseases comprise over 100 conditions, each associated with a variety of viral, bacterial, fungal and protozoan infections. M. tuberculosis and less virulent mycobacteria, such as bacille Calmette-Guérin vaccines and environmental non-tuberculous mycobacteria, may cause severe disease in patients with primary immunodeficiency diseases. However, no previous review has dealt with the issue of which primary immunodeficiency diseases predispose affected individuals to mycobacterial disease. This information is very useful, not only increasing our understanding of human immunity to mycobacteria, but also for the diagnostic investigation of patients with mycobacteriosis. We review here the medical literature on cases of mycobacterial disease in patients with primary immunodeficiency diseases.

Humans↗
PubMed2001

Impaired interferon gamma-mediated immunity and susceptibility to mycobacterial infection in childhood.

Mendelian susceptibility to poorly virulent mycobacteria such as bacillus Calmette-Guerin (BCG) and environmental nontuberculous mycobacteria is a clinically heterogeneous syndrome. The clinical features of affected children cover a continuous spectrum from disseminated lethal bacillus Calmette-Guerin infection to local recurrent nontuberculous mycobacterial infection. Different types of mutations in four genes (IFNGR1, IFNGR2, IL12B, IL12RB1) have revealed both allelic and nonallelic heterogeneity and result in eight different disorders whose common pathogenic pathway is impaired interferon gamma (IFNgamma) mediated immunity. The severity of the clinical phenotype depends on the genotype. Complete IL-12 p40 and IL-12 receptor beta1 deficiencies and partial IFNgamma receptor 1 (IFNgammaR1) and IFNgammaR2 deficiencies generally lead to curable infections at various ages, and antibiotics supplemented with IFNgamma if required are likely to be effective. Complete IFNgammaR1 and IFNgammaR2 deficiencies predispose to overwhelming infection in early childhood, which may respond to antibiotics but relapse when antibiotics are discontinued. Rapid discrimination between complete IFNgammaR1 and IFNgammaR2 deficiency and other defects, therefore, is an important diagnostic step for planning clinical management.

Child↗
PubMed2000

Antioxidative capacity in patients with common variable immunodeficiency.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation, detoxifying scavenger enzymes, and molecules with antioxidant capacity could contribute to the increased susceptibility to cancer and infections in severe humoral immunodeficiency. We studied antioxidant status, i.e., plasma antioxidant capacity (TEAC), retinol, alpha-to-copherol, ubiquinol, and the number of activated T cells in 16 patients with common variable immunodeficiency (CVID) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated HLA-DR and CD45RO-expressing T cells. Plasma levels of the endogenous ROS scavenger ubiquinol (Q 10) were significantly lower in patients as compared to controls. However, patients showed only slightly reduced levels of TEAC as well as the exogenous antioxidants retinol and alpha-tocopherol. Although no correlation of the number of activated T cells and antioxidant capacity could be demonstrated, an increase in ROS and a diminished reactive oxygen scavenger capacity may be involved in the disease process in patients with common variable immunodeficiency.

Adolescent↗
PubMed2000

Spontaneous and oxidative stress-induced programmed cell death in lymphocytes from patients with ataxia telangiectasia (AT).

T cell lymphopenia in the peripheral blood lymphocytes (PBL) of patients with AT is mainly caused by a decrease of naive CD45RA+/CD4+ cells followed by a predominance of memory CD45RO+ lymphocytes. To relate these findings to the regulation of programmed cell death, we investigated the activation state and apoptotic level of PBL in 12 patients and healthy controls by flow cytometry. In accordance with previous investigations, the number of naive CD4+/CD45RA+ cells was significantly decreased in patients compared with healthy controls. This disturbed balance of CD45RA and CD45RO was also reflected in higher amounts of activated HLA-DR and CD95 expressing cells, with a concomitant decrease of Bcl-2 protected lymphocytes in the T cell population. With regard to its role in preventing oxidative-induced cell death, we analysed Bcl-2 expression and apoptosis in the presence of oxidative stress. In culture, cells of patients are more susceptible to spontaneous programmed cell death. However, in our stress-inducing system (hypoxanthine/xanthine oxidase system) the number of cells undergoing apoptosis was lower in patients' cell populations compared with controls. In addition, preliminary results suggest that Bcl-2 expression and level of spontaneous apoptosis in patients can be modified by IL-2 and interferon-gamma.

Adolescent↗
PubMed2000

Severe adenovirus bronchiolitis in children.

UNLABELLED: Severe adenoviral infections such as the necrotizing adenovirus bronchiolitis occur sporadically in infants. Ascertaining the etiologic role of adenovirus in cases of lung disease can pose a diagnostic problem. We present two cases of severe bronchiolitis in previously healthy children in which adenovirus could be shown to be the causing agent. Both children received immunosuppressive therapy with steroids and Cyclosporin for 3 mo and a course of intravenous Ribavirin for 10 d. The results were conflicting: despite therapy Patient 1 died due to respiratory failure, Patient 2 improved notably. CONCLUSIONS: Adenovirus can cause severe bronchiolitis in previously healthy children. Diagnosis may be difficult to achieve. The role of antiviral therapy in the treatment of adenoviral infections remains to be cleared.

Adenovirus Infections, Human↗
PubMed2000

Immunogenicity and tolerance of a 7-valent pneumococcal conjugate vaccine in nonresponders to the 23-valent pneumococcal vaccine.

There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 microgram/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 microgram/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients.

Adolescent↗
PubMed1999

Anti-oxidative capacity in patients with ataxia telangiectasia.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation and detoxifying scavenger enzymes could contribute to the increased susceptibility to cancer and infections in ataxia telangiectasia. We studied oxidative status, i.e. plasma total antioxidant capacity (TEAC), retinol, alpha-tocopherol, ubiquinol, and the number of activated T cells in 10 patients with ataxia telangiectasia (AT) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated human leukocyte antigen-DR and CD45RO expressing T cells. TEAC levels as well as the exogenous antioxidants retinol and alpha-tocopherol were significantly reduced in patients. In addition, patients showed slightly reduced plasma levels of the endogenous ROS scavenger enzyme ubiquinol (Q10). Although no correlation between number of activated T-cells and antioxidant capacity could be demonstrated, an increase in ROS and a diminished reactive oxygen scavenger capacity may be involved in the disease process of patients with AT.

Adolescent↗
PubMed1999

MR high-resolution blood oxygenation level-dependent venography of occult (low-flow) vascular lesions.

A new technique for detecting vascular malformations, high-resolution BOLD venography (HRBV), is described. This technique relies on the BOLD principle for detecting deoxygenated blood in low-flow malformations. HRBV images are acquired using a modified 3D gradient-echo with voxel volumes of 0.5 x 0.5 x 2 mm3. The magnitude data are masked with the phase images to enhance visibility of the venous structures and are displayed using the minimum intensity projection. Preliminary results for 10 patients show that HRBV is more sensitive in detecting cavernomas than is T2-weighted imaging, and lesions that are presumed to be telangiectasias are detected only with this technique.

Brain↗
PubMed1998

Diagnostic evaluation of sonographically visualized breast lesions by using a new clinical amplitude/velocity reference imaging technique (CARI sonography).

RATIONALE AND OBJECTIVES: The goal of this study was to evaluate and differentiate breast lesions in patients by sonographic measurements performed using CARI sonography. METHODS: Thirty-one patients with 33 histologically proven breast lesions were examined by mammography, conventional ultrasound sonography, and CARI sonography. Investigation with mammography-like positioning was performed in case of CARI sonography. The ratios of the lesion diameters were calculated in a craniocaudal and a mediolateral plane. The results were compared with the results obtained with conventional modalities. RESULTS: Breast lesions were detected with the best sensitivity (100%) and a high specificity (86%) using B-mode ultrasound sonography. Mammography resulted in a sensitivity of 92% and a specificity of 91%, whereas the CARI sonography yielded 100% sensitivity and 67% specificity. CONCLUSIONS: The differentiation of lesions by measurements performed with CARI sonography resulted in a high sensitivity. The specificity, however, was inferior compared with the other imaging modalities. This may limit the routine application of the technique for clinical diagnoses of breast lesions. However, due to the small number of patients investigated in this pilot study, the full potential should be evaluated in a larger collective of patients.

Adult↗
PubMed1996

[MRI tomographic blood volume measurements in the diagnosis of a stroke: the results of a clinical pilot study].

PURPOSE: In this study the sensitivity of proving a stroke using regional cerebral blood volume (rCBV) maps were investigated. Another aim was to evaluate the strength of the ischaemia. METHODS: Seven patients were examined during the acute phase of a stroke, eight during the subacute or chronically stage. To calculate rCBV-maps of one slice low dosed Gd-DTPA was injected as a bolus. Using the relaxation-effect the obtained signal intensity-time curves were converted pixel-wise to rCBV images. For the region of the infarction rCBV ratios were calculated relative to the corresponding area in the contralateral hemisphere. RESULTS: Only 63% of the investigations carried out during the acute phase were utilizable. In all those cases a decrease of rCBV was found. The infarct area could only visually recognized if the rCBV ratio was lower than 0.7. The ratios of completely and partial necrotic areas of the infarctions were 0.481 and 1.028 respectively. With a p = 0.0015 these values are even statistically different. CONCLUSIONS: During the acute stage the sensitivity of the rCBV measurement was not as high as that of morphological MR imaging. However, rCBV maps make it possible to estimate the strength of the ischaemia even during the first hours.

Adult↗
PubMed1995

[Possibilities of the use of MR tomography-based cerebral blood volume maps in the diagnosis of brain tumors].

PURPOSE: Today contrast enhanced MR imaging is a reliable method for detecting mostly distinguishing between different histological types of tumours. In this study we use a MR-based method to measure the regional cerebral blood volume (rCBV). Using this technique we try to judge the grading and vitality of the tumours. METHODS: 26 patients with various types of brain tumours were examined. To calculate rCBV-maps of one slice, low-dosed Gd-DTPA was injected as a bolus. Using the relaxation effect the obtained signal intensity-time curves were converted pixel-wise into rCBV images. For the tumours rCBV-ratios were calculated relative to the corresponding area in the contralateral hemisphere. RESULTS: In the investigated group all tumours were detected on the basis of a raised rCBV-ratio. Since only vital parts of the tumour are perfused, the rCBV maps may be used to determine the place of biopsy. CONCLUSIONS: The differential diagnosis of all histological tumour types was not possible on the basis of rCBV values. Distinction between low grade and high grade gliomas was also not significant. However, a low grade glioma can be excluded if the morphological images definitely indicate an astrocytoma and if the rCBV-ratio was higher than 2.

Adult↗