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Biomedical subjects

B Hellmich

Publications and source records attributed to B Hellmich.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Wegener's granulomatosis in the head and neck region].

Wegener's granulomatosis (WG) is defined as a granulomatous inflammation of the upper and lower respiratory tract and systemic vasculitis of small and medium sized vessels which is often accompanied by a necrotizing glomerulonephritis. The etiology of the disease is still unknown. In former times untreated WG usually ended deadly. Immunosuppressive therapy made WG a treatable disease with a chronically relapsing course. Therefore an early diagnosis of WG is of utmost importance. WG usually starts as a limited and localized organ manifestation in the upper respiratory tract and it generalizes, if untreated, with pulmonary and renal involvement. Symptoms in the head and neck region are observed in up to 95% of the patients with WG. Sinusitis, crusting of the nose, development of a saddle nose, middle and inner ear symptoms and subglottic stenosis are common manifestations. Due to the early and common manifestation of WG in the head and neck region the otorhinolaryngologist plays an important role for the early diagnosis and the fast initiation of immunosuppressive therapy but also during follow-up for activity assessment.

Aged↗
PubMed2004

Autoantibodies against granulocyte-macrophage colony stimulating factor and interleukin-3 are rare in patients with Felty's syndrome.

OBJECTIVES: Antibodies against granulocyte colony stimulating factor are frequently found in patients with Felty's syndrome (FS). In this study, we examined the prevalence of antibodies against two other granulopoietic cytokines: granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL3). METHODS: Sera of 32 patients with FS, 20 normocytic patients with rheumatoid arthritis (RA), and 72 healthy individuals were screened for the presence of antibodies against GM-CSF and IL3 by ELISA and bioassays, using the human erythroleukaemia cell line TF-1. RESULTS: In two of the 32 patients with FS, antibodies to GM-CSF and IL3 were detectable by ELISA. Binding anti-GM-CSF antibodies were also detected in one of the 72 healthy controls, while in another healthy subject and in one of the patients with normocytic RA, anti-IL3 antibodies were present. Serum from one of the two patients with FS who tested positive for anti-IL3 and anti-GM-CSF antibodies by ELISA showed strong neutralising capacity to the biological effect of IL3, but not to GM-CSF in vitro. Patients with FS had significantly higher serum levels of GM-CSF (median; 2.82 pg/mL; interquartile range 2.64-3.19 pg/mL) compared with patients with RA (2.52 pg/mL; 2.28-2.72 pg/mL; p = 0.012) and healthy controls (2.23 pg/mL; 2.04-2.52; p<0.001). In addition, serum levels of IL3 in patients were significantly higher in FS (10.05 pg/mL; 8.94-11.98) compared with controls (4.79 pg/mL; 3.72-7.22; p<0.001), but not compared with RA patients (9.52 pg/mL; 8.32-10.42; p = 0.17). CONCLUSIONS: Antibodies to GM-CSF and IL3 are rare in patients with FS and RA and in healthy subjects. In individual patients with FS, the presence of neutralising anti-IL3 antibodies may contribute to the development of cytopenia.

Autoantibodies↗
PubMed2004

Churg Strauss syndrome--successful induction of remission with methotrexate and unexpected high cardiac and pulmonary relapse ratio during maintenance treatment.

OBJECTIVE: To examine the safety and efficacy of methotrexate (MTX) plus low-dose prednisolone for induction of remission in non life- or organ-threatening courses and for remission maintenance in Churg-Strauss syndrome (CSS). METHODS: In an open-label study 11 patients were treated with MTXfor induction of remission at initial diagnosis and relapse. Twenty-five patients received MTX for maintenance of remission. Primary endpoints were the achievement of remission and the incidence of relapses, respectively. Doses of concomitant prednisolone (PRD) and side effects were secondary endpoints. RESULTS: Induction of remission was achieved in 8/11 patients with MTX/PRD. Median time to remission was 5 months (range 2-9). Remission was maintained in 12 of 23 with available long-term follow-up (median 48 months). Eleven patients experienced 8 major and 3 minor relapses with a median time from remission to first relapse of 9 months. With MTX, the median cumulative PRD dose during the induction phase was 6.2 g. In the maintenance phase PRD could be reduced by 53% in responders. Apart from one case of MTX-induced pneumonitis, adverse events were confined to mild/moderate episodes of infection and leucopenia. No opportunistic infections occurred, neither did steroid-specific adverse events. CONCLUSIONS: MTX is safe and effective for the induction of remission in non-life-threatening CSS. It allows a considerable reduction of PRD and thus avoidance of PRD-related adverse events. However, the ability of MTX to prevent relapses in CSS appears limited. The identification of an optimal maintenance regimen and prognostic factors for treatment response requires trials with larger patient numbers.

Adolescent↗
PubMed2003

[Therapy of primary systemic vasculitis].

The treatment of systemic vasculitides has changed during the past ten years from a uniform immunosuppressive regimen consisting of cyclophosphamide and prednisolone to a stage- and activity-adapted, more differentiated immunosuppressive and immunomodulating therapy. Due to the low incidence of these diseases, the assessment of these regimens by prospective, randomized, controlled trials has only been enabled through multicenter cooperation. In primary systemic vasculitides of small- or medium-sized vessels induction of remission therapy comprises methotrexate in early generalized disease without significant renal insufficiency, cyclophosphamide in full-blown generalized disease and additional plasma exchanges in cases of rapidly progressive glomerulonephritis if oliguric, each in conjunction with oral prednisolone. After achievement of remission patients are switched to a less potent maintenance of remission therapy with better long-term tolerability, such as azathioprine. Glucocorticoids are the mainstay for large vessel vasculitides, supplemented by azathioprine or methotrexate in cases of critical organ perfusion or demand for high steroid doses. Therapy for secondary vasculitides relies essentially on the treatment of the underlying disease, which means virus elimination in cases of hepatitis B or C associated vasculitides. Immunosuppression in these diseases is reserved for organ- or life-threatening manifestations only.

Adjuvants, Immunologic↗
PubMed2003

[Airway manifestations of relapsing polychondritis: treatment with cyclophosphamide and placement of bronchial stents].

We report the case of a 41-year-old female patient with relapsing polychondritis and severe respiratory involvement. The patient presented with acute respiratory failure requiring endotracheal intubation. Bronchoscopy revealed tracheal collapse and inflammatory stenoses with dynamic collapse of the major airways. We describe a multidisciplinary therapeutic approach, consisting of immunosuppressive treatment, bronchoscopic placement of self-expandable stents into the collapsing bronchi, and tracheotomy. In addition, we report the effectiveness of oral cyclophosphamide for treatment of relapsing polychondritis with severe respiratory involvement after failure of other immunosuppressive agents. The problem of severe respiratory complications in patients with relapsing polychondritis and the need for a multidisciplinary approach is discussed.

Adult↗
PubMed2003

Pitfall in diagnosing growth hormone deficiency in a hypochondroplastic patient with a delayed puberty.

Hypochondroplasia is a clinically and genetically heterogeneous skeletal dysplasia with less obvious disproportion in childhood and a reduced pubertal growth spurt. We report on a young hypochondroplastic man who had been misdiagnosed and treated as being growth hormone (GH) deficient in the early phase of puberty. The delay of his puberty which is unusual in hypochondroplasia might have confused the results of provocative GH testing. At the age of 17 years measurement of body proportions revealed an increased upper to lower body segment ratio. Skeletal radiographs showed a lack of increase in the interpedicular distance from the first to the fifth lumbar vertebra, anteroposterior shortening of the lumbar pedicles, short femoral necks, a fibula longer than the tibia, and short tubular bones. As the clinical and radiographic features suggested the diagnosis of a skeletal dysplasia, a DNA sequence analysis of the fibroblast growth factor receptor 3 gene on chromosome 4 p16.3 was performed, which identified the missense mutation C1620 G in the tyrosine kinase domain resulting in an Asn540Lys substitution. Hypochondroplastic children with this common mutation (N540K) were previously found to respond to GH treatment with an increase in sitting height compared to leg length, which accentuated the existing disproportion. We want to emphasise that in children with normal serum IGF-I and IGFBP-3 levels accurate measurements of body proportions and skeletal radiographs in disproportionate cases are more important than reiterative GH stimulation tests, which prepubertally and in the early phase of puberty often show subnormal responses.

Child↗
PubMed2002

Circulating transforming growth factor beta1 (TGFbeta1) is elevated by extensive exercise.

Transforming growth factor beta1 (TGFbeta1) is a multifunctional growth factor involved in immune function, atherosclerosis, fibrotic disease, diabetic complications and bone turnover. It is synthesized in large quantities by bone cells in response to hormones and mechanical stimuli. Plasma contains inactive "latent" TGFbeta1, which consists of the precursor molecule and a TGFbeta1-binding protein. Platelets store latent TGFbeta1 in their alpha-granules, and serum therefore contains large amounts of latent TGFbeta1. We developed a technique for determining latent plasma TGFbeta1 and investigated whether circulating TGFbeta1 is affected by the stimulation of bone formation in response to strength training. Ten healthy students with low training activity participated in a heavy exercise programme over 4 weeks. Blood was drawn into citrate-filled syringes containing prostaglandin E(1) (PGE(1)) and immediately centrifuged at 4 degrees C. TGFbeta1 was determined with a sandwich ELISA standardized with National Institute for Biological Standards and Controls (NIBSC) materials. Six of the ten students completed the training. Highly reproducible values (500-600 pg/ml) of latent TGFbeta1 in plasma were determined. Baseline levels of TGFbeta1 were 525 (50) pg/ml [mean (SE)], which is in the range observed for young adults. TGFbeta1 concentrations rose significantly to 710 (65) pg/ml after 2 weeks of training and thereafter slowly declined to 650 (62) pg/ml after 2 weeks and 440 (33) pg/ml after 4 weeks, respectively. No active TGFbeta1 was detectable in citrate PGE1 plasma samples. Serum levels were between 6000 and 10,000 pg/ml and contained 200-400 pg/ml active TGFbeta1. In contrast to previous reports, plasma did not contain measurable amounts of circulating active TGFbeta1. We demonstrate that heavy exercise transiently elevates latent TGFbeta1 concentrations in plasma. TGFbeta1 is produced by osteoblasts in considerable amounts; therefore, we assume that the observed changes are partly due to enhanced TGFbeta1 production or release in bone, since the quantities of TGFbeta1 produced by other cells are comparably small.

Adult↗
PubMed2002

MRI of the pharynx and treatment efficacy of a mandibular advancement device in obstructive sleep apnoea syndrome.

In obstructive sleep apnoea syndrome (OSAS), prosthetic mandibular advancement devices (MAD) seem to be a promising treatment alternative to conventional continuous positive airway pressure therapy. Unfortunately, while they are effective in some patients, they are ineffective in others or may even worsen OSAS. At present, it is not known whether predictors can be defined which allow for estimation of the potential effect of oral appliances on the severity of OSAS. Clinical and polysomnographical efficacy of a MAD was evaluated in 15 patients with OSAS. In addition, ultrafast magnetic resonance imaging (MRI) of the pharynx was performed in 13 of these patients at rest during transnasal shallow respiration and during performance of the Muller manoeuvre, both with and without the MAD, and the site of closure was determined. The MAD reduced the mean apnoea/hypopnoea index (AHI) from 19.8+/-14.5 to 7.2+/-7.4 x h(-1). Seven subjects (53.8%) had at least a 50% reduction in AHI to a value <10 x h(-1) with the MAD, whereas the MAD was ineffective in six patients. Five of the seven treatment responders had no significant pharyngeal obstruction during the manoeuvre with the device, while all of them had pharyngeal obstruction when not equipped with the device. Four of the six patients with treatment failure had a single velopharyngeal obstruction and two a combined obstruction of the velo- and glossopharynx during the Muller manoeuvre while wearing the device. The results of this study suggest that airway patency during the Muller manoeuvre while wearing a mandibular advancement device may be predictive of the success of obstructive sleep apnoea syndrome treatment with a mandibular advancement device.

Adult↗
PubMed2001

Anti-MPO-ANCA-positive microscopic polyangiitis following subacute bacterial endocarditis.

Although infectious agents such as Staphylococcus aureus have been implicated in the pathogenesis of Wegener's granulomatosis, the role of bacterial infections in the pathogenesis of other types of small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) is less clear. We describe a patient who developed a non-granulomatous necrotising small vessel vasculitis and perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO) after recurrent episodes of bacterial endocarditis due to Staph. aureus. Although cytoplasmic ANCA (c-ANCA) directed against proteinase 3 have been reported in single patients with bacterial endocarditis, to our knowledge this patient is the first reported case of an anti-MPO-ANCA positive systemic vasculitis following bacterial endocarditis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Cytomegalovirus infection in systemic necrotizing vasculitis: causative agent or opportunistic infection?

We report on a 69-year-old woman who presented with myalgia, hearing impairment, fever, night sweats, weight loss, muscular weakness, paresthesia, hypesthesia, and hypalgesia. Sural nerve biopsy showed demyelinative and axonal polyneuropathy due to necrotizing vasculitis with fibrinoid necrosis. A positive test for antineutrophil cytoplasmic antibodies (ANCA) with a perinuclear immunofluorescence pattern directed against myeloperoxidase was more suggestive of microscopic polyangiitis (MPA) than of polyarteritis nodosa (PAN), the possible differential diagnoses. In addition, positive tests for cytomegalovirus (CMV) antibodies (immunoglobulin (Ig)M and IgG) and the detection of CMV-DNA in sputum specimens by polymerase chain reaction (PCR) were indicative of active CMV infection. Treatment with ganciclovir and anti-CMV immunoglobulin in addition to prednisolone medication for 6 months resulted in rapid improvement of the clinical symptoms without relapse. CMV infection has been described to be related to ANCA-associated vasculitis in non-immunocompromized patients and may be either a causative agent or an opportunistic infection. Identification of a viral etiology in patients with atypical ANCA-associated vasculitides may lead to different, less aggressive treatment approaches, including antiviral therapy.

Aged↗