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S Diederich

Publications and source records attributed to S Diederich.

At least 19 recordsLinked to original sources
PubMed2001

Enzyme-mediated protection of the mineralocorticoid receptor against progesterone in the human kidney.

Progesterone (P) is a mineralocorticoid (MC)-antagonist in vitro. During pregnancy, plasma P concentrations exceed aldosterone concentrations at least 50-fold, but plasma aldosterone increases only 4-8-fold in a compensatory manner. Since the in vivo anti-MC activity of P seems to be only moderate, we hypothesized that P is metabolized by enzymes of MC target tissue similar to the way cortisol is metabolized by 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2 in order to protect the MC receptor. We, therefore, examined P metabolism using 4-(14)C-P in subcellular fractions of human postmenopausal and male kidneys, and in homogenates of one premenopausal kidney. We found that P is converted effectively, even at high P concentrations (10(-6) mol/l), to various metabolites: 20alpha-dihydro(DH)-P; 17alpha-OH-P; 17alpha-OH,20alpha-DH-P; 5alpha-DH-P; 3beta,5alpha-tetrahydro(TH)-P; and 20alpha-DH,5alpha-DH-P. Homogenates of premenopausal kidney also showed conversion to 3alpha- and 5beta-reduced P metabolites. These results confirm the existence of an efficient renal enzyme system as a possible mechanism of an enzyme-mediated MC receptor selectivity.

20-alpha-Dihydroprogesterone↗
PubMed2001

[Bronchial carcinoma screening with low dosage CT. Current status].

Lung cancer is the most common cause of death from malignancy. It is characterized by a favourable prognosis when treated in early stages and a poor prognosis in advanced stages. Populations at risk are relatively well defined, i.e. heavy smokers and workers exposed to asbestos and radon. Therefore, early detection using diagnostic techniques promises reduction of mortality from this tumor. Previous studies using chest radiography and sputum cytology were, however, disappointing due to poor sensitivity of these tests for early tumor stages. The new technique of low-dose computed tomography provides both high sensitivity for small tumors and a comfortable examination. As small benign pulmonary nodules are common reliable non-invasive diagnostic algorithms are required for classification of nodules. Preliminary studies using low-dose CT screening in smokers have provided promising results. Prior to a wide application of the technique in clinical routine more data are required as to inclusion criteria, examination intervals and the effect of screening on mortality reduction.

Carcinoma, Bronchogenic↗
PubMed2001

Detection of pulmonary nodules at spiral CT: comparison of maximum intensity projection sliding slabs and single-image reporting.

The aim of this study was to compare numbers of pulmonary nodules detected with maximum intensity projections using a slab thickness of 15 mm (MIP 15) and 30 mm (MIP 30) with single image (SI) presentation of chest CT scans. Two readers reviewed MIP 15, MIP 30, and SI presentations of 10-mm (n = 8) and 5-mm collimation (n = 10) helical CT scans and recorded size, location, and diagnostic confidence (definite, probable) of pulmonary nodules. Readers 1 and 2 recorded more nodules with MIP 15 than with SI: 10-mm collimation, 77/64 and 60/56; 5-mm collimation, 64/60 and 40/36; and more "definite" nodules (10-mm collimation: 68/57 and 51/42; 5-mm collimation: 43/36 and 34/30). MIP 15 also detected more nodules than MIP 30 at 10-mm collimation: 77/72 and 60/50; with no major differences at 5-mm collimation: 64/66 and 40/38; and more "definite" nodules (10-mm collimation: 68/58 and 51/36; 5-mm collimation: 43/39 and 34/29). There were only minor differences between SI and MIP 30. Reading time and image number per study were reduced with MIP presentations by a factor of 1.4-5.3. There were no significant differences in the number of nodules detected with SI, MIP 15, and MIP 30, but MIP presentation reduced reporting time and filming cost when compared with SI reporting. For detection of nodules MIP 15 was slightly superior to MIP 30.

Adolescent↗
PubMed2001

Differential diagnosis of polyuric/polydipsic syndromes with the aid of urinary vasopressin measurement in adults.

OBJECTIVE: A water deprivation test or a hypertonic saline infusion test with the measurement of plasma osmolality and plasma vasopressin are the gold standard tests in the differential diagnosis of polyuric syndromes. Because commercially available vasopressin kits are too insensitive for this approach, and the concentration of vasopressin in urine is much higher than in plasma, urinary vasopressin measurements may be an alternative to the more difficult plasma vasopressin measurement. DESIGN: The diagnostic value of the measurement of urinary vasopressin with a rather insensitive commercially available vasopressin kit was compared with plasma vasopressin measurement by a highly sensitive radioimmunoassay (RIA). PATIENTS AND METHODS: Thirteen normal subjects and 27 patients with polyuria/polydipsia were examined by an 8-h fluid deprivation test. In all blood samples (0800 h, 1200 h, 1400 h and 1600 h) and in all urine collections (2-hourly fractions), osmolality as well as vasopressin were measured. RESULTS: Using plasma vasopressin measurement with a highly sensitive RIA as gold standard test, nine patients were classified as having primary polydipsia, whereas 18 had partial or complete cranial diabetes insipidus. Whereas the substitution of plasma vasopressin measurement by urinary vasopressin measurement alone did not provide 100% separation between both groups, the product of urinary vasopressin and urinary osmolality related to plasma osmolality completely separated the patients with primary polydipsia from those with diabetes insipidus. Urinary measurement of vasopressin and osmolality alone, which was recommended as a noninvasive diagnostic procedure in children, was too insensitive for exact differential diagnosis in our adult patients. CONCLUSIONS: The simultaneous measurement of plasma vasopressin and plasma osmolality in a dehydration test is the most powerful diagnostic tool in the differential diagnosis of polyuria/polydipsia. However, if highly sensitive assays for plasma vasopressin measurements are not available, the measurement of urinary vasopressin with commercially available, less sensitive RIAs may be a diagnostic alternative, which showed nearly the same sensitivity as plasma vasopressin measurement in our study population.

Adult↗
PubMed2001

[Radiologic screening for lung cancer: present status and future perspectives].

Radiologic screening for lung cancer: present status and future perspectives. Lung cancer is the most common cause of death from malignancy. This is predominantly due to the poor prognosis of the mostly advanced tumor stages at the time of presentation. Prognosis of early, usually asymptomatic stages is more favourable, particularly in non-small-cell histologic types. Therefore, early detection using diagnostic tests promises reduction of mortality from lung cancer. Due to its high sensitivity for small pulmonary nodules - the most common manifestation of early lung cancer - computed tomography appears suitable as a screening test particularly as the high radiation exposure associated with standard examination protocols can be significantly reduced for this purpose. Due to the high prevalence of benign small pulmonary nodules diagnostic algorithms are required for non-invasive classification of detected nodules. Preliminary studies of low-dose CT using algorithms based on size and density of detected nodules revealed a high proportion of asymptomatic lung cancers and early resectable tumor stages with a small number of invasive procedures for benign nodules. Prior to a wide application of this technique in clinical routine more data is required as to appropriate inclusion criteria, screening intervals and most importantly the effect of screening on reduction of mortality from lung cancer.

Adult↗
PubMed2001

Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues.

11beta-Hydroxysteroid dehydrogenases (11beta-HSD) are microsomal enzymes that catalyze the conversion of active glucocorticoids (GC) to their inactive 11-dehydro products and vice versa. Two isoenzymes of 11beta-HSD have been characterized and cloned in human tissues. The tissue-specific metabolism of GC by these enzymes is important for mineralocorticoid (MC) and GC receptor occupancy and seems to play a crucial role in the pathogenesis of diseases such as apparent MC excess syndrome, and may play roles in hypertension, obesity and impaired hepatic glucose homeostasis. This article reviews the literature and examines the role and importance of 11beta-HSD in humans.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Therapeutic strategies in adrenal insufficiency.

Severe chronic adrenal insufficiency (primary or secondary) is a potentially lethal disorder, unless the patient is regularly substituted with glucocorticoids, usually with hydrocortisone (15-25 mg/day) and with 9 alpha-fluor-hydrocortisone (0.05-0.2 mg/day) in addition in patients with the primary adrenal disorder (Addison's disease). In stressful situations and in febrile disorders, the glucocorticoid dosage must be increased prophylactically in order to prevent an "adrenal crisis". Most women with adrenal insufficiency will profit from the additional substitution of dehydroepiandrosterone (DHEA) with regard to well-being and sexual function. A patient with acute adrenal insufficiency will die if the diagnosis is missed and high-dose glucocorticoid treatment is not instituted immediately. Acute adrenal insufficiency developing de novo in an intensive care patient (e.g. from adrenal hemorrhage or adrenal vein thrombosis) is a most challenging diagnosis. In these patients, however, survival not only depends on glucocorticoid substitution but also on the underlying disease.

Acute Disease↗
PubMed2000

Radiation exposure associated with imaging of the chest: comparison of different radiographic and computed tomography techniques.

Exposure to ionizing radiation due to radiologic examinations is associated with the risk of induction of malignancy. This has to be balanced against the potential benefits of detection of a malignant tumor with radiologic examinations. For comparison of radiation exposure levels from different sources, the concept of effective dose equivalent was developed, which is used to assess an individual's risk of developing malignancy. Effective dose equivalent ranges from 0.06 to 0.25 millisieverts (mSv) with chest radiography in 2 views, 3-27 mSv with computed tomography (CT) using conventional examination parameters, and 0.3-0.55 mSv using low dose CT settings. These values can be compared with radiation exposure levels from natural sources (on average 2.4 mSv per year in Germany). Based on considerations by the International Commission on Radiological Protection, it can be expected that radiation exposure with an effective dose equivalent of 1 mSv would lead to 5 additional malignancies in 100,000 individuals exposed.

Dose-Response Relationship, Radiation↗
PubMed2000

Screening for asymptomatic early bronchogenic carcinoma with low dose CT of the chest.

BACKGROUND: Survival of patients with lung carcinoma is very poor, particularly for patients with advanced disease. There are no early clinical symptoms, and screening with chest radiography has not been recommended. Computed tomography (CT) is superior to radiography for detection of pulmonary nodules but usually is associated with relatively high radiation exposure. Recently, accuracy of low dose CT has been shown to be similar to conventional dose CT. The goal of the current study was to assess the findings of low dose CT of the chest in heavy smokers. METHODS: More than 700 heavy smokers (> 20 pack years; age: > 40 years) underwent unenhanced low dose CT of the chest. Detected nodules were classified according to their density (soft tissue, calcified, fat) and size (< 6 mm, 6-10 mm, > 10 mm). In nodules larger than 10 mm with no CT features to suggest a benign lesion, histology was obtained. RESULTS: In approximately 40% of smokers, nodules smaller than or equal to 10 mm were detected. None was resected. In less than 3% of individuals, lesions larger than 10 mm were detected; 8 were bronchogenic carcinoma. All eight carcinomas were resectable. Lesions for which no histology was obtained were followed with low dose CT. CONCLUSIONS: Low dose CT detected 8 bronchogenic carcinomas in more than 700 heavy smokers. All eight were resectable. Pulmonary nodules measuring up to 10 mm were found in 40% of smokers. The significance of these small lesions has remained unclear.

Adult↗
PubMed2000

Diagnostic radiation oncology: malignant cystosarcoma phylloides.

BACKGROUND: Cystosarcoma phylloides is a rare, mostly benign tumor of the breast. In most cases curative treatment is possible with complete surgical excision of the lesions. However, there is a high local recurrence rate up to 46%. There are only few reported successful treatments with radiotherapy in cystosarcoma phylloides. Radiotherapy is indicated in patients with locoregional recurrent disease and those with symptomatic metastases. PATIENT: We present a case of a 54-year-old woman with a painless mass in the right breast. Clinical examination showed a large, firm tumor and axillary lymph node metastases. The patient underwent mastectomy and axillary lymph node dissection. Histopathology showed a cystosarcoma phylloides measuring 30 x 25 x 19 cm as well as lymph node metastases measuring 9.5 cm. Despite a R0 resection the patient developed 4 thoracic wall recurrences within 2 years. At 18 months there were additional multiple pulmonary and pleural lesions with a maximum diameter of 6.5 cm. Subsequently the patient received polychemotherapy. There was a significant response of the thoracic wall disease as well as of the pulmonary and pleural lesions. Six months later there was further progress of the thoracic wall disease and the pulmonary lesions. Following this the patient underwent radiation therapy of her right thoracic wall with 50 Gy which lead clinically to a quick response. For the past 5 months there has been no evidence of thoracic wall disease recurrence. CONCLUSION: This is an unusual case of cystosarcoma phylloides and response to different therapeutic modalities. Cystosarcoma phylloides showed to be a radiosensitive tumor. Thus postopertive radiation therapy is indicated to prevent local recurrences.

Breast Neoplasms↗
PubMed2000

Spiral CT of pulmonary nodules: interobserver variation in assessment of lesion size.

The aim of this study was to assess interobserver variability in size determination of pulmonary nodules at spiral CT. Twenty-three patients with known pulmonary nodules (diameter 2-40 mm, mean diameter 7 mm) underwent spiral chest CT (collimation 5 mm, pitch 1). Images were reconstructed at 3- and 5-mm intervals (RI). Hard copies were analyzed by two radiologists who recorded every nodule with regard to location, diagnostic confidence ("definite," "probable") and nodule size in increments of 1 mm with specific attention to correct classification into one of three size classes (< or = 5 mm, 6-10 mm, > 10 mm). Interobserver variability was determined with Pearson's correlation coefficient and kappa measure. Of a total of 286 nodules, 103 nodules were found accordingly by both readers at 3 mm RI, and 96 at 5 mm RI. There was a good correlation of measurements (in millimeters) between both readers (Pearson's correlation coefficient: 0.89-0.95). Interobserver variability in categories was good at both reconstruction intervals (kappa: 0.61 at 3 mm, 0.74 at 5 mm RI) and very good (0.81) at 5 mm RI when uncertain nodules were excluded. Spiral CT allows reproducible size determination of pulmonary nodules as shown by good interobserver agreement in exact size measurement and categorization into three size classes.

Calibration↗
PubMed2000

Pulmonary manifestation of systemic mast cell disease.

Systemic mast cell disease is a rare disease of unknown aetiology. Systemic infiltration and proliferation of mast cells in skin, bone marrow, gastrointestinum and lymph nodes is the central pathological feature. This study reports a patient with mastocytosis of the skin (urticaria pigmentosa) for 10 yrs. The patient was referred to hospital for dyspnoea. Chest radiograph showed moderate reticular infiltration of both lungs, computerized tomography revealed multiple lymph nodes of the mediastinum and faint nodular lesions of middle and upper areas of lungs. Transbronchial biopsy demonstrated mast cell infiltration of the lung with formation of mast cell granuloma. According to the current literature, systemic mast cell disease with pulmonary involvement is a very rare entity. After a treatment with interferon alpha-2a over 6 months, the patient's condition and particularly dyspnoea showed improvement in parallel with an amelioration of the lesions as demonstrated by thorax computed tomography.

Humans↗
PubMed2000

11Beta-hydroxysteroid-dehydrogenase isoforms: tissue distribution and implications for clinical medicine.

11Beta-hydroxylation is essential for glucocorticoid and mineralocorticoid activity of a steroid. The enzyme catalyzing this reaction is termed 11beta-hydroxysteroid-dehydrogenase (11beta-HSD). Two isoenzymes of 11beta-HSD have been characterized in human tissues. Whereas 11beta-HSD-I works mainly as a reductase, 11beta-HSD-II only functions as an oxidizing (inactivating) enzyme for physiological glucocorticoids. Thus, the tissue distribution of both enzymes plays a crucial role for the specific glucocorticoid status of an organ. This review summarizes our knowledge of tissue distribution of both 11beta-HSD isoenzymes, their physiological function and pathophysiological role in certain clinical abnormalities, and their relevance to the metabolism of synthetic glucocorticoid and mineralocorticoid compounds.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2000

Selenium-based digital radiography in the detection of bone lesions: preliminary experience with experimentally created defects.

PURPOSE: To compare the diagnostic performance of selenium-based digital radiography with that of conventional screen-film radiography and storage phosphor radiography for the detection of bone lesions simulating osteolyses. MATERIALS AND METHODS: Artificial osseous lesions 1.0-3.0 mm in diameter were created in 80 of 160 predefined regions in 16 porcine femoral specimens. Specimens were enclosed in containers filled with paraffin to ensure accurate repositioning and to obtain an absorption condition comparable to that of a human extremity. Imaging was performed with a selenium-based digital radiography system, a conventional screen-film system, and a storage phosphor radiography system with an exposure identical to that used during clinical imaging. The presence of a lesion was assessed with a five-point confidence scale. Receiver operating characteristic (ROC) analysis was performed for a total of 1,440 observations (480 per modality), and diagnostic performance was estimated with the area under the ROC curve (A(z)). Differences in diagnostic performance were assessed with the paired Student t test. RESULTS: ROC analysis results showed A(z) values of 0.656 for selenium-based digital radiography, 0.679 for storage phosphor radiography, and 0.680 for conventional screen-film radiography. Differences between the three modalities were not significant (P =.60-.93). CONCLUSION: Image quality with selenium-based digital radiography was comparable to that with conventional screen-film radiography and storage phosphor radiography.

Animals↗
PubMed2000

Primary hyperaldosteronism without suppressed renin due to secondary hypertensive kidney damage.

Primary hyperaldosteronism is characterized by high plasma and urinary aldosterone and suppressed PRA. Renin suppression is due to aldosterone-dependent sodium retention and mild extracellular volume expansion. We observed three patients with primary hyperaldosteronism, severe refractory hypertension, and normal to high normal PRA levels whose aldosterone/renin ratios were still elevated because of disproportionately high aldosterone levels. All available medical data on the patients as well as publications on the aldosterone/renin relationship in primary hyperaldosteronism were reviewed to explain the unusual findings. In one patient, histologically proven renal arteriolosclerosis was the probable cause of the escape of PRA from suppression by an aldosterone-producing adenoma. In the other two patients, hypertensive kidney damage due to primary hyperaldosteronism was the most likely explanation for the inappropriately high PRA, as in patient 1. All patients had high normal or slightly elevated serum creatinine levels and responded to 200 mg spironolactone/day with increased serum creatinine and hyperkalemia. Hyperkalemia was probably due to a decreased filtered load of sodium and a spironolactone-induced decrease in mineralocorticoid function. Two patients were cured of hyperaldosteronism by unilateral adrenalectomy but still need some antihypertensive therapy, whereas one patient has probable bilateral adrenal disease, with normal blood pressure on a low dose of spironolactone. In patients with severe hypertension due to primary hyperaldosteronism, PRA can escape suppression if hypertensive kidney damage supervenes. An increased aldosterone/PRA ratio is still useful in screening for primary hyperaldosteronism. These patients may respond to spironolactone therapy with a strong increase in serum creatinine and potassium. Early specific treatment of primary hyperaldosteronism is therefore indicated, and even a patient with advanced hypertension will profit from adrenalectomy or cautious spironolactone treatment.

Aldosterone↗
PubMed2000

In the search for specific inhibitors of human 11beta-hydroxysteroid-dehydrogenases (11beta-HSDs): chenodeoxycholic acid selectively inhibits 11beta-HSD-I.

OBJECTIVE: Selective inhibitors of 11beta-hydroxysteroid-dehydrogenase type I may be of therapeutical interest for two reasons: i) 9alpha-Fluorinated 11-dehydrosteroids like 11-dehydro-dexamethasone (DH-D) are rapidly activated by human kidney 11beta-hydroxysteroid-dehydrogenase type II (11beta-HSD-II) to dexamethasone (D). If the same reaction by hepatic 11beta-HSD-I could be selectively inhibited, DH-D could be used for selective renal immunosuppressive therapy. ii) Reduction of cortisone to cortisol in the liver may increase insulin resistance in type 2 diabetes mellitus, and inhibition of the enzyme may lead to a decrease in gluconeogenesis. Therefore, we characterized the metabolism of DH-D by human hepatic 11beta-HSD-I and tried to find a selective inhibitor of this isoenzyme. METHODS: For kinetic analysis of 11beta-HSD-I, we used microsomes prepared from unaffected parts of liver segments, resected because of hepatocarcinoma or metastatic disease. For inhibition experiments, we also tested 11beta-HSD-II activity with human kidney cortex microsomes. The inhibitory potency of several compounds was evaluated for oxidation and reduction in concentrations from 10(-9) to 10(-5)mol/l. RESULTS: Whereas D was not oxidized by human liver microsomes at all, cortisol was oxidized to cortisone with a maximum velocity (V(max)) of 95pmol/mg per min. The reduction of DH-D to D (V(max)=742pmol/mg per min, Michaelis--Menten constant (K(m))=1.6 micromol/l) was faster than that of cortisone to cortisol (V(max)=187pmol/mg per min). All reactions tested in liver microsomes showed the characteristics of 11beta-HSD-I: K(m) values in the micromolar range, preferred cosubstrate NADP(H), no product inhibition. Of the substances tested for inhibition of 11beta-HSD-I and -II, chenodeoxycholic acid was the only one that selectively inhibited 11beta-HSD-I (IC(50) for reduction: 2.8x10(-6)mol/l, IC(50) for oxidation: 4.4x10(-6)mol/l), whereas ketoconazole preferentially inhibited oxidation and reduction reactions catalyzed by 11beta-HSD-II. Metyrapone, which is reduced to metyrapol by hepatic 11beta-HSD-I, inhibited steroid reductase activity of 11beta-HSD-I and -II and oxidative activity of 11beta-HSD-II. These findings can be explained by substrate competition for reductase reactions and by product inhibition of the oxidation, which is a well-known characteristic of 11beta-HSD-II. CONCLUSIONS: Our in vitro results may offer a new concept for renal glucocorticoid targeting. Oral administration of small amounts of DH-D (low substrate affinity for 11beta-HSD-I) in combination with chenodeoxycholic acid (selective inhibition of 11beta-HSD-I) may prevent hepatic first pass reduction of DH-D, thus allowing selective activation of DH-D to D by the high affinity 11beta-HSD-II in the kidney. Moreover, selective inhibitors of the hepatic 11beta-HSD-I, like chenodeoxycholic acid, may become useful in the therapy of patients with hepatic insulin resistance including diabetes mellitus type II, because cortisol enhances gluconeogenesis.

11-beta-Hydroxysteroid Dehydrogenases↗