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B Hellmich

Publications and source records attributed to B Hellmich.

44 records · Page 3Linked to original sources
PubMed2000

Activation of transforming growth factor-beta1 in diabetic kidney disease.

Recent data have suggested that certain growth factors and cytokines are involved in the development of diabetic nephropathy. The aim of this study was to investigate whether circulating transforming growth factor beta 1 (TGF-beta1) and tumor necrosis factor alpha (TNF-alpha) are associated with diabetic kidney disease. Serum levels of active and total TGF-beta1 and TNF-alpha were measured in type 2 diabetic patients with nephropathy (n = 23) or without (n = 35) and normoglycemic controls (n = 12). Serum levels of circulating active TGF-beta1 were significantly higher in patients with diabetic nephropathy (0.43 +/- 0.06 ng x mL(-1)) compared with diabetic patients without renal involvement (0.23 +/- 0.03 ng x mL(-1), P = .002) and healthy controls (0.24 +/- 0.03 ng x mL(-1), P= .001), whereas the levels of total (active + latent) TGF-beta1 were not different between the subgroups. Active TGF-beta1 concentrations were correlated with urinary albumin excretion (r = .49, P < .003) and serum creatinine (r= .55, P < .01). Sera from patients with type 2 diabetes contained significantly more TNF-alpha than sera from normoglycemic controls (3.07 +/- 0.24 v 1.65 +/- 0.20 pg x mL(-1), P = .001). However, the comparison of serum TNF-alpha concentrations between microalbuminuric and normoalbuminuric diabetic patients showed no significant difference (3.21 +/- 0.28 v 2.97 +/- 0.34 pg x mL(-1), P = .12). In conclusion, type 2 diabetic patients with diabetic nephropathy exhibit increased activation of TGF-beta1, in serum, suggesting an association between circulating TGF-beta1 activity and the development of renal disease.

Aged↗
PubMed2000

Granulocyte-macrophage colony-stimulating factor (GM-CSF) but not granulocyte colony-stimulating factor (G-CSF) induces plasma membrane expression of proteinase 3 (PR3) on neutrophils in vitro.

The theoretical risk of triggering vasculitis resulting from administration of G-CSF and GM-CSF to patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), such as Wegener's granulomatosis (WG), who develop agranulocytosis due to cytotoxic therapy, is unknown. Since there is strong evidence that activation of polymorphonuclear neutrophils (PMN) induced by binding of ANCA to PR3 or myeloperoxidase (MPO) expressed on their plasma membrane is involved in the pathogenesis of systemic vasculitides (SV), we studied the surface expression of PR3 and MPO on PMN from healthy donors in response to G-CSF and GM-CSF in vitro by flow cytometric analysis. Increasing doses of G-CSF did not alter PR3 expression on either untreated or tumour necrosis factor-alpha (TNF-alpha)-primed donor PMN significantly. In contrast, GM-CSF significantly increased PR3 membrane expression on both intact PMN and neutrophils primed with TNF-alpha. MPO expression was not significantly altered by either G-CSF or GM-CSF. In summary, these data demonstrate that GM-CSF, but not G-CSF, induces plasma membrane expression of PR3 on PMN in vitro. Since in AAV accessibility of the antigen (PR3 or MPO) to the antibody (ANCA) on the plasma membrane of PMN is thought to be essential for neutrophil activation by ANCA, the results of the present study suggest that administration of GM-CSF to patients with WG with neutropenia implies a definite theoretical risk of deterioration of vasculitis via this mechanism.

Adult↗
PubMed1999

Granulocyte colony-stimulating factor treatment for cyclophosphamide-induced severe neutropenia in Wegener's granulomatosis.

OBJECTIVE: To examine the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in the treatment of cyclophosphamide (CYC)-induced severe neutropenia (<1,000 neutrophils/microl) in patients with generalized Wegener's granulomatosis (WG). METHODS: Six WG patients with severe neutropenia due to CYC treatment (group A) were given short-term dosages of rHuG-CSF. Treatment response in these 6 patients was compared with that in 6 WG patients who were matched for age, sex, disease status, and prior treatment and who received supportive treatment only (group B). RESULTS: The duration of severe neutropenia was significantly shorter in group A patients (4.0+/-0.8 days) than in group B patients (9.0+/-1.3 days; P = 0.03). This was accompanied by fewer bacterial infections (2 versus 4) and fewer nonbacterial infections (0 versus 3) in group A compared with group B patients. Treatment with rHuG-CSF was well tolerated and, notably, no disease flare occurred during treatment and up to 4-6 months after rHuG-CSF administration. CONCLUSION: Short-term, low-dose rHuG-CSF treatment can substantially shorten the duration of CYC-induced neutropenia and appears to confer significant clinical benefit. Such treatment, aimed at raising the neutrophil count above 1,000/microl, does not appear to carry a high risk of inducing a flare of the vasculitis.

Adult↗
PubMed1999

Treatment of severe neutropenia due to Felty's syndrome or systemic lupus erythematosus with granulocyte colony-stimulating factor.

OBJECTIVES: To examine the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for the treatment of severe neutropenia due to Felty's syndrome (FS) or systemic lupus erythematosus (SLE). METHODS: Eight patients with absolute neutrophil counts (ANC) below 1,000/microL attributable to FS (n = 4) or SLE (n = 4) were treated with rhG-CSF. The hematologic and clinical response as well as side effects were recorded. In addition, reports on the use of rhG-CSF/rhGM-CSF in FS and SLE retrieved from the English language literature were analyzed. RESULTS: RhG-CSF effectively corrected neutropenia due to FS and SLE in seven of the current eight patients. In 54 of 55 FS and SLE patients retrieved from the literature, G-CSF or GM-CSF, respectively, proved to be effective at elevating the neutrophil count, which was often associated with improvement of infectious complications. The neutrophil count often declined again when growth factor treatment was stopped but generally stabilized at a level that exceeded the pretreatment count. Side effects included rare cases of thrombocytopenia, arthralgias, and development of cutaneous leukocytoclastic vasculitis. Side effects were dose dependent and resolved when treatment was discontinued. One of our own patients and 17 previously reported patients continued to benefit from long-term administration of rhG-CSF over periods of more than 40 months. CONCLUSIONS: RhG-CSF is an effective and generally well-tolerated treatment for neutropenia due to FS or SLE. Exacerbation of the underlying rheumatic condition due to G-CSF appears to be rare if G-CSF is administered at the lowest dose effective at elevating the ANC above 1,000/microL.

Adult↗
PubMed1997

NG-nitro-L-arginine methyl-ester: a muscarinic receptor antagonist?

The effect of the nitric oxide synthase inhibitor NG-Nitro-L-arginine methyl ester (L-NAME) towards muscarinic receptors was studied in vitro and in vivo. L-NAME displaced the antimuscarinic ligand [3H]quinuclidinyl benzilate ([3H]QNB) from its specific binding sites in rat cerebral cortex and cerebellum homogenates with a more than 10,000 fold lower affinity than atropine, pirenzepine and AFDX 116. Data for L-NAME binding were best fit according to a two-site model (Kd 7.2 nM and 3,000 nM) in the rat cerebellum, whereas in rat cortex a one-site model (Kd 1670 nM) was superior. In anesthetized rats and rabbits L-NAME (7.5-185 mumol/kg) attenuated a hypotensive response to Acetyl beta-methyl-choline (Ac beta-Me Ch)(6.25 nmol/kg) in a dose related fashion, but this effect was negligible as compared to that of atropine (8.8 and 17.7 nmol/kg). Furthermore, the effect of L-NAME was not specifically antimuscarinic since its attenuating effect against ATP- or histamine-induced responses was not statistically different from that of Ac beta-Me Ch. A vagus stimulation induced bradycardia was entirely uninfluenced by L-NAME (37 mumol/kg). In isolated bladder experiments (rabbit) we demonstrated a complete lack of efficacy of L-NAME against Ac beta-Me Ch induced contractions. In the pithed rat preparation L-NAME was ineffective against the MeN-A-343 induced pressor responses. In summary, we demonstrated that the nitric oxide synthase inhibitor L-NAME shows very weak affinity at M1- and M2-receptors in the rat brain in vitro, but appears to have no significant antimuscarinic properties against M1-, M2- and M3-receptor mediated effects in rats and rabbits in vivo.

Animals↗
PubMedDate not supplied

Update on the pathogenesis of Churg-Strauss syndrome.

Churg-Strauss syndrome (CSS) is a rare form of systemic vasculitis occurring in patients with asthma. The cause of CSS is unknown, and yet little data are available regarding its pathogenesis. The presence of a marked tissue- and blood-eosinophilia, as well as secretory products of eosinophils in blood and tissues, implicates a pathogenetic role of eosinophil granulocytes. Prolonged survival of eosinophils due to inhibition of CD95-mediated apoptosis by soluble CD95 seems to contribute to eosinophilia in CSS. Although the mechanisms involved in eosinophil-activation in CSS have not been elucidated, recent data suggest a possible role of T lymphocytes secreting eosinophil-activating cytokines. This review describes the current insights into the pathogenesis of CSS in the light of its putative nature as a type 2 granulomatous disease. Recent clinical, experimental and epidemiologic data regarding the possible role of inflammatory cells and their secretory products, anti neutrophil cytoplasm antibodies (ANCA), epidemiologic factors and anti-asthma treatments are summarized.

Churg-Strauss Syndrome↗
PubMedDate not supplied

Remission in antineutrophil cytoplasmic antibody-associated systemic vasculitis.

The definition of remission in patients with systemic vasculitis must be distinguished from the term "cure," which implies that patients are well and not requiring ongoing therapy. Remission should be defined using a standardised approach to measuring clinical disease activity, and the definition should be qualified by the duration of the remission and the type of maintenance therapy required to sustain remission. Remission is an important goal of management in the systemic vasculitides and is achievable in most patients. Maintenance of remission is a more difficult target, and evidence from studies of patients with antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis indicates that durable, lasting remission is unlikely to occur. Despite good disease control, damage or scarring from disease or its treatment is a common finding and is a separate outcome from remission. Future studies of vasculitis therapies should address the concept of rapid and sustained disease control, so that patients spend most of their time in a state of good health, with minimal damage.

Antibodies, Antineutrophil Cytoplasmic↗