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Biomedical subjects

H M Steffen

Publications and source records attributed to H M Steffen.

At least 19 recordsLinked to original sources
PubMed2006

Impact of inhibitors of the Renin-Angiotensin-aldosterone system on liver fibrosis and portal hypertension.

Morbidity and mortality of chronic liver disease are primarily caused by liver cirrhosis and portal hypertension, both of them secondary disorders of progressive liver fibrosis. The main fibrogenic cell type in the liver, the hepatic stellate cell (HSC), is activated and stimulated by several factors, among which the renin-angiotensin-aldosterone system (RAAS) plays a major role. Angiotensin II induces various profibrotic pathways via the angiotensin II receptor type 1 (AT(1) receptor) not only in heart and kidney, but also in liver tissue. Stimulation of the AT(1) receptor promotes the transformation of the quiescent HSC into the myofibroblast like activated HSC and the synthesis of transforming growth factor-beta1 (TGF-beta), the major profibrotic cytokine in the liver. In addition, aldosterone has been suggested to induce profibrotic effects in chronic heart and liver disease. This review focuses on the concept that inhibitors of the RAAS retard or even reverse liver fibrosis and reduce portal hypertension. Angiotensin converting enzyme (ACE) inhibitors, AT(1) receptor antagonists, and aldosterone antagonists have been demonstrated to reduce the proliferation of HSC, to decrease the synthesis of profibrotic molecules, and to have the potential to improve liver fibrosis. However, side-effects such as systemic hypotension may impair the clinical application of RAAS inhibitors in patients with liver cirrhosis and portal hypertension. Also, efficacy may be limited by the downregulation of AT(1) receptors in advanced fibrosis, which has been observed in animal and human studies. Randomized clinical studies are essential to evaluate, whether this approach is beneficial in patients with chronic liver disease and progressive fibrosis.

Drug Design↗
PubMed2002

[Development of ultrasonography in a radiological university department from 1994 to 2001].

BACKGROUND: In 1994, 5 % of a total of 25 718 examinations and 7 % of all 4630 B-mode sonograms performed in the Radiology Department, University of Cologne was classified as not indicated. In light of these results, the health care policy guidelines for sonographic indications have been amended. PURPOSE: The aim of this study was to establish the current rate of non-indicated sonographic examinations performed in routine diagnostics by radiology departments at university hospitals, to determine the reasons for such over-diagnosis and identify which regulatory mechanisms can be implemented to prevent his. METHOD: We counted the number of 1) B-mode and 2) color-flow Doppler ultrasound imaging procedures carried out in patients who had had no change in symptoms within the previous 4 weeks or who were scheduled without reference to an existing sonogram (double examinations). 3) The reasons for over-diagnosis were analyzed. 4) The 1994 survey was repeated in 2000 with an identical protocol and 5) additionally, a modified survey of the diagnostic questions was conducted. RESULTS: 1) Out of 4,119 patients presenting for the first time to receive a B-mode sonogram, 443 prior sonograms (11 %), 305 CT scans (7 %) and 57 MRI scans (1 %) were documented. 2) Double sonograms were carried out in 6 % of the 1,118 patients presenting for the first time for color-flow Doppler ultrasounds and in 16 % of the 651 patients assigned to receive catheter angiographies with arterial color-flow Doppler. 2) 41 out of 55 (75 %) prior sonograms from non-university settings stated by 94 surgery patients were listed in the medical records. 36 out of 43 (84 %) prior sonograms from the university hospital were repeated in the same patients despite the fact that the medical report with the findings was available. None of the 48 sonograms indicated to confirm a plausible finding yielded any information that was additionally relevant to therapy. 4) In the period April - June, 2000, 12 % of all 15,921 tests and interventions, 26 % of 3,569 B-mode sonograms and 58 % of 1,033 abdominal sonograms performed in adults were classified as having not been indicated. 5) Staging and follow-up were stated as the most common reasons that a sonography was carried out in 46 % of the 1,017 adults who were given B-mode sonograms conducted from Jan - Mar, 2000 and comprised 62 % of the 410 sonograms classified as not or probably not medically indicated. CONCLUSION: The results showed that a multidisciplinary consensus was required to establish the diagnostic value of sonographic procedures. Therefore, this research group drafted a hospital-internal interdisciplinary guideline for "abdominal transcutaneous B-mode sonography in oncological questions".

Diagnostic Imaging↗
PubMed1999

[The Cologne Guidelines Conference: computer-assisted clinical practice guidelines in clinical diagnosis].

Eighteen clinical practice guidelines on interdisciplinary diagnostic issues were developed at the University Hospital of Cologne, Germany. The guideline committee is organized and directed by the quality control program, which also includes the local Cochrane initiative and a wide range of organizational topics. During guideline development, questions of differential diagnosis were addressed to the same extent as the organizational and financial realization. Broad consideration was given to medicolegal implications, but need for interspecialty cooperation was judged to be more critical and even more relevant in this regard. Guidelines were primarily developed as algorithms and translated to text versions secondarily. Critical steps in the decision tree were supported by rated literature and recommendations weighte by criteria as used in evidence-based medicine. For implementation, guidelines were presented to colleagues in a series of short lectures, as print versions containing all literature used in the developing process, and in hypertext format, which is accessible via intranet. Three levels of presentation were chosen in the html-version: algorithm, decision, and information. The former is due to orientation in the guideline, the second displays the binary question, and the latter makes the scientific background available, together with literature and links for more information. Efforts to check effectiveness are currently been made, questions of efficiency will be addressed in future.

Algorithms↗
PubMed1997

Invasive amoebiasis in two patients with AIDS and cytomegalovirus colitis.

Homosexual persons or human immunodeficiency virus (HIV)-infected patients frequently excrete cysts of nonpathogenic strains of Entamoeba histolytica ("Entamoeba dispar"). However, invasive amoebiasis is rare. We report two patients with AIDS and cytomegalovirus colitis in whom invasive amoebiasis was histologically diagnosed. It is concluded that E. histolytica has to be considered in HIV-infected patients with colitis.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Secondary amyloidosis in ulcerative colitis--successful treatment with colchicine].

A 20 year old male patient with a four-years-history of moderately active ulcerative colitis was admitted due to extensive generalized edema. He suffered from a nephrotic syndrome, which was caused by secondary renal amyloidosis due to the colitis. Under continuous low dose therapy with colchicine in addition to the usual colitis therapy proteinuria decreased from values above 10 g/die to about 3 g/die and edema disappeared completely. Secondary amyloidosis following inflammatory bowel disease is a rare event, in case of ulcerative colitis a true curiosity. Cases published so far are discussed.

Adult↗
PubMed1995

[Autonomic failure as the cause of vertigo and syncope].

BACKGROUND: Vertigo and syncope often occur during orthostatic conditions. A possible cause is asympathicotonic dysregulation with a fall of blood pressure and no increase in heart rate. After the exclusion of secondary disturbances of autonomic innervation. g. in diabetes mellitus, and pharmacological side effects, e.g. tricyclic antidepressants, primary reasons must be considered. We present 2 cases of primary autonomic failure. PATIENTS: Patient 1 had Parkinson-syndrome, impaired bladder function and orthostatic dysregulation with a maximal drop of blood pressure to 60/40 mm Hg. Patient 2 showed orthostatic dysregulation with a minimal blood pressure of 70/30 mm Hg without further symptoms, in a tilt table examination catecholamines were measured during orthostatic conditions. Patient 1 had normal, and patient 2 very low resting catecholamine plasma levels. Neither patient reacted with a rise of plasma catecholamines when tilted to an upright position. These findings are diagnostic of multiple system atrophy (MSA) in patient 1 and pure autonomic failure (PAF) in patient 2. DISCUSSION: In PAP only dysautonomic symptoms are found. It has a favourable prognosis. MSA consists of an autonomic dysregulation in combination with parkinsonism, cerebellary and bulbar symptoms, prognosis quo ad vitam is poor. Diagnosis is often established by a tilt table examination and radiology findings, and is often late. Treatment of both diseases consists of pharmacological, e.g. fludrocortisone, vasopressin analogues and ergotamine tartrate as well as non-pharmacological blood pressure stabilizing measures.

Adult↗
PubMed1995

Plasma catecholamines, thrombocyte alpha 2- and lymphocyte beta 2-adrenoceptor densities in hypertensive patients with low or normal plasma renin concentrations.

The sympathetic nervous system is unique in the regulation of plasma renin, for it can stimulate or suppress renin release by activation of either renal beta- or alpha 2-adrenoceptors. The authors studied plasma renin concentration (PRC), noradrenalin and adrenalin levels in plasma, and the densities of lymphocyte beta 2-adrenoceptors and thrombocyte alpha 2-adrenoceptors in 25 hypertensive patients with either normal (11-40 mU/L; n = 9) or low PRC (0-10 mU/L; n = 14). There were no differences in plasma catecholamine levels and adrenoceptor densities between the two patient groups. A positive correlation (r = 0.66; P < 0.005) between beta 2-adrenoceptor density and PRC in the patient group with low PRC, and a negative correlation (r = -0.72; P < 0.01) between alpha 2-adrenoceptor density and plasma renin in patients with normal PRC were found. They conclude that adrenoceptor densities on blood elements and plasma catecholamines do not differ in low and normal renin hypertension. The significant correlations between adrenoceptor densities and PRCs may indicate that adrenoceptors on blood elements mirror adrenoceptor densities in the kidney and that tonic suppression of renin release through alpha 2-adrenoceptors is preserved in hypertensive patients with normal plasma renin levels.

Adult↗
PubMed1994

Changes in plasma norepinephrine concentration and thrombocyte alpha 2-adrenoceptor density during long-term antihypertensive therapy with nitrendipine and captopril.

Antihypertensive drugs influence the sympathetic nervous system in different ways that may cause adverse or beneficial effects. We treated 48 hypertensive patients with either nitrendipine (10-20 mg twice daily, b.i.d.) or captopril (25-50 mg b.i.d.) for 16 weeks to evaluate changes in plasma catecholamines, platelet alpha 2- and lymphocyte beta 2-adrenoceptors. Blood pressure (BP) decreased from 153/95 to 135/87 mm Hg with captopril and from 155/99 to 137/89 mm Hg with nitrendipine. Treatment with nitrendipine significantly stimulated plasma norepinephrine (NE) from 327 +/- 37 to 446 +/- 50 pg/ml, and treatment with captopril resulted in a significant reduction in platelet alpha 2-adrenoceptor density from 265 +/- 39 to 171 +/- 26 fmol/mg protein. Despite having equal BP-lowering properties, captopril and nitrendipine have different effects on the sympathetic nervous system. Stimulation of plasma NE during long-term treatment with nitrendipine may contribute to possible adverse effects, whereas reduction in alpha 2-adrenoceptors induced by captopril may contribute to the vasodilating effect of angiotensin-converting enzyme (ACE) inhibition.

Adult↗
PubMed1994

Reduced lymphocyte beta 2-adrenoceptor density and impaired diastolic left ventricular function in patients with glucocorticoid deficiency.

OBJECTIVE: Patients with adrenal crisis are at risk of severe hypotension not responding to administration of catecholamines. As glucocorticoids may be a prerequisite for intact beta-adrenoceptor function, impaired adrenoceptor activity may explain the hypotension and reduced cardiac performance in adrenal insufficiency. The aim of our study was, therefore, to further elucidate the permissive action of glucocorticoids on adrenergic function and cardiac performance. DESIGN: Prospective randomized controlled study. PATIENTS: Nine patients with adrenal insufficiency were investigated before and 48 hours after glucocorticoid withdrawal. Mineralocorticoid therapy remained unchanged during the study period. MEASUREMENTS: Lymphocyte beta 2-adrenoceptor density, intracellular c-AMP response to isoprenaline, platelet alpha 2-receptor density, plasma catecholamines, serum cortisol, plasma ACTH, echocardiography. RESULTS: Glucocorticoid depletion was demonstrated by a fall in serum cortisol from mean +/- SEM 441 +/- 62 to 45 +/- 18 nmol/l. Glucocorticoid withdrawal decreased lymphocyte beta 2-receptor density from 798 +/- 111 to 498 +/- 54 binding sites/cell (P < 0.05) and the intracellular c-AMP response to isoprenaline from 15.0 +/- 4.2 to 8.2 +/- 1.7 pmol/10(6) cells (P < 0.05). Echocardiography showed impaired diastolic relaxation after glucocorticoid withdrawal with prolongation of the rapid filling period (80.3 +/- 12.5 vs 138.3 +/- 11.8 ms, P < 0.05). Plasma catecholamines, platelet alpha 2-receptor density and systolic left ventricular function were not affected by glucocorticoid deficiency. CONCLUSIONS: This study demonstrates the importance of normal glucocorticoid levels for beta 2-adrenoceptor function and helps to explain the decreased responsiveness to catecholamines and the impaired cardiac performance in adrenal crisis.

Adolescent↗
PubMed1994

Plasma catecholamines and adrenoceptors in young hypertensive patients.

An elevated sympathoadrenal tone and an imbalance in postsynaptic alpha- and beta-adrenoceptor function are discussed as factors in the pathogenesis of essential hypertension. This study examined plasma catecholamines, thrombocyte alpha2-adrenoceptors and lymphocyte beta2-adrenoceptors in 16 young patients with newly detected essential hypertension and 26 normotensive age matched controls (27.1 +/- 4.5 vs. 24.8 +/- 2.8 years; NS). Plasma noradrenaline (276 +/- 34 vs. 216 +/- 18 pg/ml, P < 0.05) and plasma adrenaline (96 +/- 15 vs. 31 +/- 4 pg/ml, P < 0.0001) were significantly elevated in hypertensive patients. Thrombocyte alpha2-adrenoceptor density was only nonsignificantly decreased (230 +/- 37 vs. 311 +/- 36 fmol/mg protein, NS), whereas lymphocyte beta2-adrenoceptor density was markedly reduced (15.3 +/- 2.3 vs. 22.6 +/- 1.8 fmol/mg protein, P < 0.01) in hypertensive patients. Elevated plasma catecholamines are consistent with a pathophysiological role for increased sympathetic neural activity in young hypertensive patients. Assuming that results of adrenoceptor studies on blood elements are applicable on vascular receptors, our results are consistent with an imbalance of postsynaptic adrenoceptor functions which promotes the pressor effects of the sympathetic system.

Adult↗
PubMed1993

Effect of short-term antihypertensive therapy on left ventricular wall tension. A double-blind comparison of isradipine and nifedipine.

The comparative efficacy of the calcium antagonists isradipine and nifedipine in reducing left ventricular peak systolic wall tension was assessed in 25 patients with essential hypertension (20 men, 5 women; mean age: 49 years). After 2 weeks of treatment with either isradipine (2.5 mg twice daily) or slow-release nifedipine (20 mg twice daily), blood pressure was similarly reduced in both groups of patients whereas the thickness of the interventricular septum and left ventricular free wall did not change. Echocardiographic end-diastolic volume of the left ventricle showed no change whereas end-systolic volume significantly decreased with isradipine, but not with nifedipine retard. This led to a significant reduction in peak systolic wall tension in the isradipine group, but not in the nifedipine group. In conclusion, antihypertensive treatment with isradipine produces a reduction in peak systolic wall tension which is not seen with nifedipine, probably because of its negative inotropic effect.

Cardiac Volume↗
PubMed1991

[Disordered alpha 2-adrenoreceptor function in hemodialysis patients with renal anemia--a possible cause of increased blood pressure in relation to recombinant human erythropoietin?].

Nine patients on maintenance hemodialysis and transfusion-demanding renal anemia (group A) were treated with rHuEPO 120 IU/kg i.v. three times per week. Hemoglobin-content was raised from 7.2 +/- 0.9 to 10.4 +/- 0.8 g/dl. In all patients blood pressure rose, three patients developed arterial hypertension. Mean diastoloic blood pressure was 66 +/- 12 and 78 +/- 16 mmHg (p less than 0.001) before and after rHuEPO. Rise in blood pressure was accompanied by a significant fall in plasma-noradrenaline-levels (from 498 +/- 100 to 383 +/- 75 pg/ml; p less than 0.05) and alpha 2-adrenoceptor-density (from 574 +/- 76 to 384 +/- 49; p less than 0.05). Compared to nine patients on maintenance hemodialysis and hematocrit over 30% (group B), patients with severe renal anemia (group A before treatment) had higher densities of alpha 2-adrenoceptors (574 +/- 76 vs. 218 +/- 32; p less than 0.001) despite higher plasma-noradrenaline-levels (498 +/- 100 vs. 399 +/- 63; n.s.). We suppose a anemia-related disturbance of alpha 2-receptor-function with the result of abolished receptor down-regulation and impaired vascular reagibility to vasoconstricting stimuli. With the correction of anemia receptor-function improves, receptor down-regulation as well as vascular reagibility is re-established resulting in augmented vascular resistance and higher blood pressure.

Adult↗