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Biomedical subjects

W J Schnedl

Publications and source records attributed to W J Schnedl.

At least 37 records · Page 2Linked to original sources

Smooth muscle cell migration promoting activity of plasma predicts restenosis in patients with peripheral arterial occlusive disease undergoing angioplasty.

BACKGROUND: Efficacy of percutaneous transluminal angioplasty (PTA) is limited by restenosis occurring in a large proportion of patients. Smooth muscle cell (SMC) migration is a major pathomechanism of restenosis. We studied SMC migration inducing activity of plasma from patients with peripheral arterial occlusive disease (PAOD) undergoing PTA. METHODS AND RESULTS: SMC migration was determined in a two-dimensional assay system after addition of 1/25 plasma dilutions. Mean increase in migration area was 65.5 +/- 33.8% in normal controls and 67.7 +/- 53.2% in patients with PAOD. 6 hours after PTA, plasmatic migration inducing activity was largely unchanged. In 19/30 patients with restenosis (6 months after PTA) migration promoting activity (82.7 +/- 60.0) was significantly higher than in 11/30 patients with patent vessels (41.8 +/- 21.0; p = 0.03). No correlation of clinical risk factors with outcome was observed. A weak correlation was found between plasmatic migration promoting activity and levels of epidermal growth factor and transforming growth factor-beta. CONCLUSION: The capacity of human plasma to stimulate SMC migration in tissue culture can be used to assess the risk for restenosis after PTA in patients with PAOD.

Aged↗

[Development of insulinoma cells as therapy in insulin-dependent diabetes mellitus].

In healthy persons insulin secreting beta-cells of the pancreas regulate blood glucose levels within a narrow physiological range. Since the detection of insulin in 1922 by Banting and Best, subcutaneous insulin replacement has remained the sole treatment modality for insulin-dependent diabetes mellitus (IDDM). However, even trained patients undergoing intensive insulin therapy fail to achieve normal function of the pancreatic beta-cells. One approach to solve this problem is pancreas and islet cell transplantation. Because of technical problems, limited number of transplantable organs and toxicity of immunosuppressive therapy, both are still in an experimental state. An alternative approach is the development of genetically modified insulin secreting cell lines for replacement of islet cells. So far, experiments support the expectation to develop genetically manipulated cell lines who imitate the function of islet beta-cells and are protected from the immune response. The ultimate goal is the development of an engineered human beta-cell line and, after animal experiments, to use it for treatment of patients with IDDM.

Animals↗

Bone scintigraphy and magnetic resonance imaging in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is an acute systemic inflammatory disorder of unknown origin. We report a patient whose AOSD presented with the commonly accepted diagnostic clinical signs and laboratory parameters. The painful joints distinctly demonstrated increased uptake of 99mTc-methylene diphosphonate in scintigraphy and areas of increased gadolinium-enhanced signal in MRI. Biopsies indicated bone marrow edema. AOSD in association with bone marrow edema had not been previously demonstrated. AOSD is often diagnosed after a considerable delay, bone scintigraphy, and magnetic resonance imaging may offer new imaging techniques for early diagnosis and successful therapy in follow-up examinations.

Adult↗

Visualization of non-Hodgkin's lymphoma by high dosed somatostatin receptor specific scintigraphy and extended single photon emission tomography.

The study aimed to increase the sensitivity of somatostatin receptor (SR) specific scintigraphy for the detection of non-Hodgkin's lymphoma (NHL). Ten selected patients presenting with histologically proven NHL and with 50% to 100% bone marrow involvement were injected with 20 micrograms octreotide labeled with a mean of 254 MBq 111In. The results were recorded with a double head gamma camera by long-time SPET (60 sec per frame, 3 interval) of neck/thorax and abdomen/pelvis. To show bone marrow displacement by lymphoma cells, SPET of the same regions (15 sec per frame, 3 interval) was recorded 3 to 7 days later after i.v. administration of 0.5-1 mg monoclonal anti-granulocyte antibody (Mab 250/183) labeled with a mean of 454 MBq 99mTc. This modality showed a person related sensitivity of 70%, a lesion related sensitivity of 48% (29/60), 60% (22/37) above and 30% (7/23) below the diaphragm. The sensitivity in detecting bone marrow involvement was 10%. Only 80% bone marrow infiltration with lymphoma cells in nodular configuration was shown by In-111-octreotide scintigraphy correlating with cold lesions in the anti-granulocyte scan. There was no false positive result; the smallest lesion correctly identified by SR scintigraphy had with a diameter of 1 cm, the largest lesion missed measured 3.5 cm. In conclusion, doubling the doses of octreotide and radiolabel and extended SPET recording improved to some extent the patient related sensitivity and visualized nodular bone marrow involvement in 10% of patients. The lesion related sensitivity improved mainly above but not below the diaphragm.

Bone Marrow↗

Effect of steroid treatment on the migration behaviour of neutrophils in patients with early rheumatoid arthritis.

The influence of methylprednisolone on the migratory characteristics of neutrophil granulocytes was investigated in 10 patients with early rheumatoid arthritis (RA) and compared to 12 controls. The migration of neutrophils was measured with a whole-blood membrane filter assay with and without stimulation by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP). Total migration index (TMI), distribution characteristics (DC) and the product of TMI and DC (neutrophil migratory activity; NMA) served to characterize the migratory behaviour of neutrophils. The data demonstrated an increased polymorphonuclear leucocyte (PMN) migration in patients with early RA, indicating a bystander role of PMNs in inflammatory joint injury. Treatment with methylprednisolone reduced significantly the penetration depth (DC) of neutrophils, but did not influence the number of migrating cells (TMI). The unstimulated NMA was significantly reduced due to the marked DC reduction, whereas steroids did not influence the stimulated NMA of neutrophils. A significant reduction in PMN penetration depth was demonstrated only after a steroid therapy of at least 10 days, suggesting that a longer period of steroid therapy is necessary to provide effective inflammatory control.

Aged↗

Haemoglobin O Padova and falsely low haemoglobin A1c in a patient with type I diabetes.

Glycated haemoglobin (HbA1c) measured by high performance liquid chromatography (HPLC) in a 20 year old female with insulin dependent diabetes mellitus was consistently within the normal range although her daily blood glucose values were > 11.1 mmol/l. HbA1c measured by immunoagglutination and fructosamine was elevated and correlated with the patient's blood glucose values. The HPLC chromatogram showed an additional peak at HbA0. Electrophoresis of haemoglobin on citrate agar gel revealed an abnormal haemoglobin anodal of HbS. Cellulose acetate electrophoresis and isoelectric focusing demonstrated an additional haemoglobin migrating close to HbA2. Amino acid analysis and DNA sequencing revealed an alpha 30 (B11) Glu-->Lys replacement, that is, haemoglobin O Padova. Investigations of two family members without diabetes revealed the same rare haemoglobin variant. This case showed that this silent haemoglobin mutation caused an additional peak and falsely low HbA1c values when measured by HPLC, the gold standard for this evaluation.

Adult↗

Evidence of accelerated gastric emptying in longstanding diabetic patients after ingestion of a semisolid meal.

UNLABELLED: This study investigated the prevalence of accelerated gastric emptying in 40 consecutive nonselected patients with longstanding insulin-dependent diabetes mellitus (range 11-54 yr; mean 27 yr). METHODS: The gastric emptying of a semisolid meal labeled with 99mTc was continuously recorded with a dual-head gamma camera for 90 min in patients who were supine. RESULTS: Eleven patients demonstrated delayed gastric emptying, but three male diabetics showed accelerated gastric emptying with retention values that were different from controls already after 10 min of recording (89% +/- 3% versus 96% +/- 4%; p < 0.02). During the 90-min segment, accelerated gastric emptying reduced initial gastric contents to 11% +/- 8% (p < 0.001) as compared to 50% +/- 10% in control subjects and 78% +/- 6% (p < 0.001) in patients with delayed gastric emptyings. Accelerated gastric emptying was characterized by an almost equal initial meal distribution in proximal and distal compartments of stomach, both emptying approximately 90% of their contents within 90 min. Normal and delayed gastric emptying was characterized by a 60%-40% initial ratio of meal distribution between gastric compartments. During normal emptying, both compartments reduced contents with approximately 50%, but delayed gastric emptying was caused by only a 15% reduction of proximal contents accompanied by a 34% reduction in distal contents. CONCLUSION: Recording in the supine position to abolish gravitational influences demonstrated accelerated gastric emptying of a firm semisolid meal with a prevalence of 8%. However, delayed gastric emptying was shown as the predominant gastric manifestation of longstanding insulin-dependent diabetes mellitus with a prevalence of 28%.

Case-Control Studies↗

[Glycosylated hemoglobin and glycosylated proteins for metabolic control of diabetes mellitus].

The target of therapy in patients with diabetes mellitus is preventing the development of late complications due to nearly normal blood glucose values. For the diagnosis and control of therapy in routine management of diabetes mellitus, determination of glycated haemoglobin (HbA1c) and fructosamine in addition to blood glucose values are of equal importance. This report stresses the clinical use, standard-determination methods and interpretation of glycated protein values. The problems of haemoglobin variants detected in Austria interfering with determination of HbA1c using the high performance liquid chromatography method and the suggestions of the American Diabetes Association for using glycated haemoglobin and fructosamine are discussed as well.

Blood Glucose↗

[Insulin producing cells as therapy in diabetes mellitus].

Even with intensive insulin therapy it is impossible to reach physiological blood glucose levels in insulin-dependent diabetes mellitus. Because of the high costs and technical problems involved in islet cell transplantation broad applicability of this therapy seems uncertain. An alternative approach is the development of molecular-engineered insulin-producing clonal cell lines. The main interest is in rodent insulinoma cell lines and neuroendocrine AtT-20ins cells. This paper reviews the current knowledge about glucose-stimulated insulin secretion and the problems that have to be solved before these cells can be used for therapy in diabetes mellitus.

Animals↗