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Biomedical subjects

K Schulte

Publications and source records attributed to K Schulte.

At least 19 recordsLinked to original sources
PubMed2001

Lycobetaine acts as a selective topoisomerase II beta poison and inhibits the growth of human tumour cells.

The phenanthridine alkaloid lycobetaine is a minor constituent of Amaryllidaceae. Inhibition of cell growth was studied in the clonogenic assay on 21 human tumour xenografts (mean IC(50) = 0.8 microM). The growth of human leukaemia cell lines was also potently inhibited (mean IC(50) = 1.3 microM). Athymic nude mice, carrying s.c. implanted human gastric tumour xenograft GXF251, were treated i.p. with lycobetaine for 4 weeks, resulting in a marked tumour growth delay. Lycobetaine was found to act as a specific topoisomerase II beta poison. In the presence of calf thymus DNA, pure recombinant human topoisomerase II beta protein was selectively depleted from SDS-gels, whereas no depletion of topoisomerase II alpha protein was observed. In A431 cells immunoband-depletion of topoisomerase II beta was induced, suggesting stabilization of the covalent catalytic DNA-intermediate in living cells. It is reasonable to assume that this mechanism will cause or at least contribute significantly to the antitumour activity.

Alkaloids↗
PubMed2001

Renal transplantation in a patient with hypocomplementemic urticarial vasculitis syndrome.

We describe a 36-year-old man who presented with hypocomplementemic urticarial vasculitis syndrome (HUVS) with severe renal involvement. Despite steroid therapy, the patient developed end-stage renal disease (ESRD) leading to chronic hemodialysis therapy. Renal transplantation was performed after hemodialysis therapy (secondary), and the patient developed a typical HUVS relapse 9 months after transplantation despite conventional immunosuppressive therapy that was successfully treated with plasma exchange. This case shows for the first time that HUVS can induce severe renal involvement responsible for ESRD and that HUVS can relapse after renal transplantation. It also suggests that plasma exchange therapy may be of value for rapidly controlling the clinical symptoms.

Adult↗
PubMed2001

Grading of internal carotid artery stenosis: validation of Doppler/duplex ultrasound criteria and angiography against endarterectomy specimen.

OBJECTIVES: duplex ultrasound has replaced angiography prior to carotid endarterectomy (CEA) in many institutions. However, the indications for CEA are based on angiographically controlled studies and widely accepted ultrasound criteria do not exist. Consequently, the reliability of Doppler and/or duplex ultrasound to predict a high-grade ICA stenosis has to be proven. DESIGN: prospective validation study. MATERIALS: one hundred and fifty carotid bifurcations assessed by ultrasound and selective angiography and 68 acrylat outcasts of carotid specimen after eversion CEA. METHODS: ICA stenosis was measured angiographically according to the ECST criteria. Combined Doppler acoustic standard criteria (CDASC), peak systolic frequency (PSF), peak systolic velocity (PSV) and end-diastolic velocity (EDV) served as criteria for the ultrasound assessment. These criteria and the results of angiography were compared to the degree of ICA stenosis determined by specimen measurements. RESULTS: the median degree of ICA stenosis as assessed by angiography (82%, range 56-97%) and CDASC (83%, range 50-99%) corresponded well to the specimen measurements (80%, range 50-95%). The sensitivity of angiography and CDASC to predict a 70-90% ICA stenosis (ECST criteria) compared to the specimen measurements was 88% and 95%, respectively. The positive predictive value (PPV) reached 92% and 96%, respectively. CDASC were equivalent to angiography and were superior to the best single frequency or velocity parameters. If CDASC do not indicate a >/=70% ICA stenosis in spite of a PSV >/=180 cm/s and/or an EDV >/=50 cm/s, angiography may detect patients with a >70% ICA stenosis. CONCLUSIONS: CDASC are valid in the quantification of high-grade ICA stenosis. They are more reliable than single velocity and/or frequency measurements. However, if velocity criteria and CDASC do not agree, angiography should be performed.

Angiography↗
PubMed2000

High prevalence of celiac sprue-like HLA-DQ genes and enteropathy in patients with the microscopic colitis syndrome.

OBJECTIVE: Celiac sprue is associated with specific HLA-DQ genes (mainly DQ2). Because there are epidemiological and histopathological similarities between celiac sprue and microscopic colitis, we hypothesized that these syndrome may share an HLA genetic predisposition and pathogenesis. METHODS: The HLA-DQ genes of 25 patients with celiac sprue, 53 patients with the microscopic colitis syndrome, and 429 normal controls were typed and compared. Serum was analyzed for antigliadin and antiendomysial antibodies. Small intestinal biopsies were analyzed for signs of histopathology. RESULTS: HLA-DQ2 or DQ1,3 (the latter as DQ1,7,DQ1,8, or DQ1,9) were seen more frequently in both patient groups relative to controls. In patients with the microscopic colitis syndrome, serological tests for celiac sprue were weakly positive in 17%; mild inflammation of the small intestine without villous atrophy was present in 43%, and inflammation plus partial or subtotal villous atrophy was present in 27%. CONCLUSIONS: A shared set of predisposing HLA-DQ genes account for the epidemiological overlap of celiac sprue and microscopic colitis. Mild to moderate mononuclear cell inflammation of the small intestine, often accompanied by partial or subtotal villous atrophy, is frequent in patients with the microscopic colitis syndrome. Although further studies will be necessary to determine if this enteropathy is induced by dietary gluten, we speculate that the small intestinal but not colonic histopathology in patients with microscopic colitis is caused by immunological gluten sensitivity.

Adult↗
PubMed1998

Retinal capillary density in patients with arterial hypertension: 2-year follow-up.

BACKGROUND: Arterial hypertension is known to be an important risk factor for cerebral and cardiovascular disease. Previous studies have demonstrated a decrease of capillary density in the perifoveal network in tandem with decreased capillary flow velocity in patients with essential hypertension. In a prospective study we quantified the retinal microcirculation in order to evaluate the time course of changes in the perifoveal network. METHODS: Thirty-three patients with essential hypertension (mean age 45 +/- 14 years) underwent video-fluorescein angiographic studies at baseline and at 2 years 28 +/- 6 months) thereafter. The angiograms were obtained with a scanning laser ophthalmoscope and were digitally recorded. By means of digital image analysis we quantified off-line the mean area of perifoveal intercapillary areas (PIA) and the mean capillary flow velocity. RESULTS: At baseline, the patients with hypertension showed significantly increased PIA and a significantly decreased capillary flow velocity compared with reference values. During the follow-up period the capillary flow velocity decreased further significantly, whereas the PIA showed no significant change. CONCLUSIONS: The continuous decrease of capillary flow velocity demonstrates a progression of altered microcirculation in patients with essential hypertension whose blood pressure was believed to be well controlled. Further studies with this technique may be useful to determine the influence of antihypertensive therapy and may help to identify patients at risk for cerebrovascular events.

Blood Flow Velocity↗
PubMed1998

Acute effect of metipranolol on the retinal circulation.

AIM: To assess the effect of topical and systemic application of a beta adrenergic receptor blocker on retinal haemodynamics. METHODS: 24 healthy subjects were included in this double masked, randomised, placebo controlled crossover study. Metipranolol, a non-selective beta adrenergic receptor blocking agent was used as test drug. In all subjects arm-retina time, arteriovenous passage time, arterial mean dye velocity, the arterial vessel diameters, and capillary flow velocity were quantified from digital video fluorescein angiograms. RESULTS: A significant effect was observed on the arteriovenous passage time (p < 0.05), the arterial mean dye bolus velocity (p < 0.05), and capillary blood velocity (p < 0.05), but not on the arterial vessel diameter. The arterial mean dye bolus velocity and capillary blood velocity increased after application of the test drug (topical and systemic). In tandem with this a decrease of the arteriovenous passage time was observed. The perfusion pressure increased after topical application and remained unchanged after systemic application of metipranolol. CONCLUSIONS: This study shows that systemic as well as topical application of metipranolol leads to increased retinal blood flow velocities. The implications of these results for treatment with beta adrenergic receptor blockers is not clear. However, in view of these data it is very unlikely that treatment with metipranolol has a negative effect on retinal blood flow.

Administration, Oral↗
PubMed1998

Pilomatricoma in elderly individuals.

We report on 4 elderly patients aged 54-85 years with histopathologically diagnosed pilomatricoma who had been seen in our department from 1993 to 1997. Pilomatricoma is a rather uncommon neoplasm in middle-aged and old patients. It is much better known in children. Here, we clinically studied these 4 cases of pilomatricoma in elderly patients (above 50 years of age) to show the variety of clinical differential diagnosis and discuss the clinicopathological features. The results of the present study indicate that the differential diagnosis of pilomatricoma should also be considered in elderly individuals.

Adolescent↗
PubMed1997

Thromboxane A2 induces cell signaling but requires platelet-derived growth factor to act as a mitogen.

This study investigates thromboxane A2-induced cell signaling and mitogenesis of bovine coronary artery smooth muscle cells. The thromboxane mimetic U 46619 [(15S)-hydroxy-11,9-(epoxymethano) prosta-5Z,13E-dienoic acid] (10 microM) stimulated [Ca2+]i signals, phosphorylation of MAP kinase (mitogen-activated protein kinase), and expression of c-fos mRNA in smooth muscle cells. In contrast, no stimulation of DNA synthesis or cell proliferation by U 46619 was observed. However, platelet-derived growth factor-BB (20 ng/ml)-induced mitogenesis was potentiated by U 46619. Similar results were obtained with I-BOP [1S-(1 alpha,2 beta(5Z),3 alpha(1E,3R*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo [2.2.1] heptan-2-yl]-5-heptenoic acid]. These potentiating effects were abrogated by a specific thromboxane receptor antagonist, suggesting that the potentiation of platelet-derived growth factor-BB-induced smooth muscle cell mitogenesis by U 46619 and I-BOP was mediated by thromboxane receptors. It is concluded that thromboxane A2 generated by blood platelets at the site of vessel injury induces cell signaling in smooth muscle cells but acts as a mitogen only in the presence of growth factor(s).

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

[Variability of perifoveal microcirculation in healthy probands].

BACKGROUND: Fluorescein angiography with a scanning laser ophthalmoscope allows the assessment of retinal hemodynamics. Fundamental for all interpretations of the evaluated data is the knowledge of the physiological variation. In the present study we examined the variability of dynamic and morphologic retinal blood flow indices in healthy subjects over a period of one year. PATIENTS AND METHODS: In sixteen healthy volunteers aged from 23 to 34 years video-fluorescein angiography was repeated nine times in one year. At each term arm-retina-time, arteriovenous passage time, mean arterial dye velocity and capillary flow velocity were assessed. In addition the perifoveal intercapillary areas and the foveal avascular zone were determined at the first and last examination. RESULTS: Statistical analysis of the evaluated data did not show any significant variation of the mean values during the one year follow-up. Reliability indices between 0.61 and 0.87 underline a stable position of each subject to the other participants at the single terms. CONCLUSION: The present study demonstrates that retinal hemodynamics are stable over a one year follow-up in healthy subjects. There are not significant changes to expect in retinal hemodynamics assesses in healthy subjects in one year under constant conditions. The knowledge of the intra- and interindividual variation of retinal blood flow indices allows a correct interpretation of pathophysiologic and pharmacological changes in retinal macro- and microcirculation.

Adult↗
PubMed1996

Retinal hemodynamics during increased intraocular pressure.

The pathogenesis of primary chronic open-angle glaucoma (POAG) remains uncertain. It has been proposed that some of these patients may present with a deficiency in retinal hemodynamic autoregulation. It is also thought that visual field loss in POAG could be related to poor retinal perfusion. The present study was undertaken to evaluate the capacity of retinal autoregulation to maintain constant retinal circulation despite an acute rise in intraocular pressure (IOP). A total of 22 healthy subjects were recruited to this study. Retinal hemodynamics were assessed by digital video fluorescein angiograms using a scanning laser ophthalmoscope at normal (13.8 +/- 1.5 mmHg) and increased IOP (33.8 +/- 3.4 mmHg). Suction cups were used for raising the IOPs. The angiograms were performed at baseline and after 1 min of increased IOP. To quantify retinal hemodynamics the arm-retina time (ART) and arteriovenous passage time (AVP) were evaluated. The ART increased significantly from 9.4 +/- 1.8 to 11.8 +/- 2.2 s (P < 0.05) during elevated IOP, and the AVP was significantly prolonged from 1.6 +/- 0.4 to 3.0 +/- 0.8 s (P < 0.01) with IOP elevation as well. The increase in ART and AVP indicates an insufficiency of retinal autoregulation after an acute rise in IOP, even in healthy subjects. It appears that IOP values of > or = 30 mmHg may be detrimental to retinal perfusion in normals as well as in patients with POAG, who may have compromised retinal perfusion to begin with.

Adult↗
PubMed1996

Gangliosides GM1, GM2 and GM3 inhibit the platelet-derived growth factor-induced signalling transduction pathway in vascular smooth muscle cells by different mechanisms.

Gangliosides appear to regulate proliferation of different cell types. In the present study, we investigated the effects of gangliosides GM1, GM2 and GM3 on platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell (VSMC) growth. In addition, we examined the effects of gangliosides on the PDGF-BB-dependent signalling transduction pathway in rat aortic VSMC. GM2 and GM1 inhibit the PDGF-BB-dependent receptor tyrosine autophosphorylation, stimulation of the PLC-gamma 1, increase of inositol-1,4,5-trisphosphate (InsP3), elevation in cytosolic free Ca2+ ([Ca2+]i), expression of the immediate early growth response gene c-fos and cell proliferation with the following rank order of potency GM2 > GM1. Although GM3 did not influence the PDGF-BB-dependent receptor autophosphorylation and PLC-gamma 1 activation, it effectively inhibited the PDGF-BB-dependent InsP3 formation, [Ca2+]i and cell growth. Binding studies with 125I-PDGF-BB on VSMC in the presence and absence of 10 to 50 microM of each ganglioside revealed that GM1 and GM2 effectively inhibited the specific binding of PDGF-BB with an IC50 value of 20 microM for GM2 and 30 microM for GM1. GM3 had no significant effect on the specific 125I-PDGF-BB binding. These observations suggest that GM1 and GM2 may interact with PDGF-BB or its receptor resulting in a prevention of its binding. GM3 was able to suppress the PDGF-BB-dependent increase of InsP3 and [Ca2+]i downstream of the PDGF-BB-dependent receptor autophosphorylation and PLC-gamma 1 activity.

Animals↗
PubMed1995

[Retinal hemodynamics in patients with hyperviscosity syndrome].

BACKGROUND: The hyperviscosity syndrome (e.g. plasmacytoma, cryoglobulinaemia and Waldenström's macroglobulinaemia) leads through the polymerisation of macro-molecules to an increased blood viscosity. This may result in microcirculatory disturbances in various organs. In the retina the hyperviscosity produces a pattern of retinal changes including dot and blot hemorrhages, retinal and optic nerve head edema and increased diameters of the veins. In the present study we quantified the retinal hemodynamic in patients with hyperviscosity syndrome. PATIENTS AND METHODS: Fifteen patients aged between 35 and 72 years were included in the study. Ten presented with Waldenström's macroglobulinaemia, two with cryoglobulinaemia and three with plasmacytoma. All patients underwent video fluorescein angiographic studies. The arteriovenous passage time (AVP) representing the retinal microcirculation and the arm retina time (ART) were quantified from the angiograms. In addition, hematocrit (Hct) and the plasma viscosity (ETA) were measured. RESULTS: The AVP was significantly prolonged in patients with hyperviscosity syndrome in comparison to healthy volunteers (AVP: 2.6 +/- 1.5 s vs. 1.6 +/- 0.4 s; p < 0.05). The ART showed no significant differences. Plasma viscosity was doubled in the patients as compared with reference values (ETA: 2.54 +/- 2.23 mPas vs. 1.24 +/- 0.08 mPas; p < 0.01). CONCLUSIONS: The simultaneous rising of plasmaviscosity and arteriovenous passage time suggests that the increase of plasmaviscosity causes retinal circulatory disturbance. All this may result in the typical fundus changes in patients with hyperviscosity syndrome.

Adult↗
PubMed1995

Retinal hemodynamics in patients with chronic open-angle glaucoma.

Recently it has been demonstrated that retinal hemodynamics are disturbed in patients with chronic open-angle glaucoma. As the underlying cause a reduction in perfusion pressure due to increased intraocular pressure (IOP) and deficiencies of retinal autoregulation has been discussed. The present study was undertaken to clarify the influence of filtering surgery on retinal hemodynamics in patients with chronic open-angle glaucoma. A total of 17 patients with chronic open-angle glaucoma aged between 37 and 86 years were included in this prospective study. All patients underwent digital fluorescein angiography before and 10 days after fistulating procedures. From the angiograms the arteriovenous passage time (AVP) and arterial mean dye-bolus velocity (MDV) were quantified by means of digital picture analysis. At baseline the AVP was significantly prolonged in the patients as compared with reference values (AVP, 2.5 +/- 0.8 versus 1.6 +/- 0.4 s; P < 0.01). After the fistulating procedure (IOP: before, 29 +/- 5 mmHg; after, 16 +/- 4 mmHg) the AVP was significantly reduced as compared with baseline values (AVP, 2.5 +/- 0.8 versus 2.0 +/- 0.4 s; P < 0.05), whereas the MDV showed only a slight increase (MDV, 5.70 +/- 0.89 versus 5.99 +/- 0.92 mm/s; P > 0.05). This study confirms a disturbance of retinal hemodynamics in patients with chronic open-angle glaucoma. The significant reduction in AVP observed after lowering of the IOP by fistulating procedures demonstrates the positive influence of IOP reduction on the retinal circulation. The improvement in retinal circulation may prevent the occurrence of further glaucomatous damage after fistulating procedures.

Adult↗
PubMed1994

Hemodilution therapy in central retinal vein occlusion. One-year results of a prospective randomized study.

Systemic hemorheologic abnormalities may play a part in the pathogenesis of central retinal vein occlusions. A statistically significant elevation of plasma viscosity was found in patients with acute central retinal vein occlusion compared with control patients. Local retinal blood flow parameters including arteriovenous passage time and mean arterial dye bolus velocity were significantly altered in the central retinal vein occlusion patients compared with age-matched controls at baseline examination. We performed a randomized, prospective, single-blind clinical investigation to determine the effect of hemorheological manipulation on the clinical course and retinal blood flow of eyes with central vein occlusion. Hemodilution included plasma expansion with hydroxyethyl-starch, withdrawal of whole blood if the hematocrit was above 42%, and rheologic manipulation with parenteral pentoxifylline. We found a statistically significant improvement in visual acuity at 1 year post-treatment for the treated group compared with the control group (increase of visual acuity of 1.5 lines vs decrease of 1.5 lines). The retinal blood flow parameters were markedly improved soon after the institution of therapy, and this may have contributed to the improvement in visual acuity in the treated group. There was no statistically significant difference between the two groups in the progression to ischemic central vein occlusion.

Aged↗
PubMed1994

Quantification of retinal capillary density and flow velocity in patients with essential hypertension.

Arterial hypertension is known to be an important risk factor for cerebral and cardiovascular disease. Previous studies in rats have demonstrated that changes in both capillary density and vessel diameter may contribute to increased vascular resistance in hypertension. In vivo studies of human subjects with essential hypertension revealed a reduction in the number of arterioles in the skin and conjunctiva; no other in vivo data are available from other tissues. By means of a new imaging technique, capillary density and capillary blood flow velocity can now be assessed in the human retina. We undertook the present investigation to determine whether patients with essential hypertension and only minor clinical retinal vascular alterations have decreased retinal capillary density and altered capillary flow velocity. Seventeen hypertensive patients with only minor retinal vascular alterations and 17 healthy volunteers matched for age were selected. All study participants underwent ophthalmologic examination and fluorescein angiographic studies by means of scanning laser ophthalmoscopy. Capillary density and capillary blood flow velocity in the perifoveal network were evaluated from the angiograms. The retinal microcirculation in the perifoveal capillary network of hypertensive patients showed significant alterations. Both the capillary density and capillary flow velocities were significantly reduced compared with the control group. For the first time alterations of capillary blood flow and capillary density in a vascular network very similar to that of the brain have been demonstrated in hypertensive patients in vivo. Further studies with this technique may help identify patients at high risk for cerebrovascular diseases.

Adult↗
PubMed1994

[Effect of hemodilution on retinal hemodynamics in retinal branch vein occlusion].

The aim of hemodilution therapy in branch retinal vein occlusion is to lower the hematocrit (HCT) and plasma viscosity and thus to ameliorate perfusion of the affected areas. In this study we compared the influence of hemodilution therapy on the retinal hemodynamics of affected areas with unaffected areas. Thirty patients with branch vein occlusion (duration of symptoms less than 14 days) aged 40-84 years (mean 63 +/- 11 years) were examined. All patients received iso- (HCT > or = 42%) or hypervolemic (HCT < 42%) hemodilution with hydroxyethyl-starch (MW 200,000/0.5 10%, HAES-steril) for 10 days. Retinal hemodynamics were quantified by means of video fluorescein angiography assessing arteriovenous passage time (AVP) of the affected and unaffected branches. Hemodilution resulted in a significant decrease in hematocrit, plasma viscosity and erythrocyte aggregation. The arteriovenous passage time of the affected area improved significantly (before therapy 4.91 +/- 2.2 s, after therapy 3.9 +/- 1.6 s). The unaffected branch showed no significant change in the arteriovenous passage time (1.85 +/- 0.7 s before and 1.79 +/- 0.7 s after therapy). The decrease in AVP in the affected branch indicates ameliorated perfusion in the affected branch area without changing the retinal hemodynamics in unaffected areas.

Adult↗