Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 289 records · Page 16Linked to original sources

PubMed1999

[Skin necrosis in the front foot area during anticoagulation with phenprocoumon].

HISTORY AND ADMISSION FINDINGS: A 52-year-old woman was admitted because of pain for several days in the lower left leg and increasing pretibial swelling with livid discoloration. Six months before she had undergone a bilateral adnexectomy with removal of the omentum and subsequent chemotherapy for ovarian cancer. INVESTIGATIONS: Duplex sonography on the day of admission revealed thrombosis of the left popliteal vein with an unobstructed femoral vein. Both the quick value (89%) and partial thromboplastin time (PTT, 35.9 s) were within normal limits. Computed tomography and sonography were highly suspicious of a local recurrence of the ovarian cancer with peritoneal carcinomatosis. TREATMENT AND COURSE: PTT-effective heparinization (heparin-Na) was initiated together with overlapping anticoagulation with phenprocoumon (thromboplastin time 20-30%). On the 9th day after starting phenprocoumon painful, black necrotic changes began to appear on the skin of the left first to fourth toes. Assuming these to be due to phenprocoumon, anticoagulation was switched to low-molecular heparin (Enoxaparin), and antithrombin III and protein C were administered. A few days later thrombosis of the right iliac vein occurred, probably caused by local recurrence of the ovarian cancer. No palliative chemotherapy was undertaken in view of the thrombotic complications. The patient died a few months later from the cancer. CONCLUSION: If there is an underlying malignancy, chemotherapy and therapeutic vitamin-K antagonism in the presence of thromboembolic complications increases the risk of lowering protein C activity and may cause the rare complication of skin necrosis, induced by phenprocoumon.

Anticoagulants↗

PubMed1999

A role for rho-kinase in rho-controlled phospholipase D stimulation by the m3 muscarinic acetylcholine receptor.

Stimulation of phospholipase D (PLD) by membrane receptors is now recognized as a major signal transduction pathway involved in diverse cellular functions. Rho proteins control receptor signaling to PLD, and these GTPases have been shown to directly stimulate purified recombinant PLD1 enzymes in vitro. Here we report that stimulation of PLD activity, measured in the presence of phosphatidylinositol 4,5-bisphosphate, by RhoA in membranes of HEK-293 cells expressing the m3 muscarinic acetylcholine receptor (mAChR) is phosphorylation-dependent. Therefore, the possible involvement of the RhoA-stimulated serine/threonine kinase, Rho-kinase, was investigated. Overexpression of Rho-kinase and constitutively active Rho-kinase (Rho-kinase-CAT) but not of kinase-deficient Rho-kinase-CAT markedly increased m3 mAChR-mediated but not protein kinase C-mediated PLD stimulation, similar to overexpression of RhoA. Expression of the Rho-inactivating C3 transferase abrogated the stimulatory effect of wild-type Rho-kinase, but not of Rho-kinase-CAT. Recombinant Rho-kinase-CAT mimicked the phosphorylation-dependent PLD stimulation by RhoA in HEK-293 cell membranes. Finally, the Rho-kinase inhibitor HA-1077 largely inhibited RhoA-induced PLD stimulation in membranes as well as PLD stimulation by the m3 mAChR but not by protein kinase C in intact HEK-293 cells. We conclude that Rho-kinase is involved in Rho-dependent PLD stimulation by the G protein-coupled m3 mAChR in HEK-293 cells. Thus, our findings identify Rho-kinase as a novel player in the receptor-controlled PLD signaling pathway.

Cell Membrane↗

PubMed1999

Regulation of muscarinic acetylcholine receptor sequestration and function by beta-arrestin.

After activation, agonist-occupied G protein-coupled receptors are phosphorylated by G protein-coupled receptor kinases and bind cytosolic beta-arrestins, which uncouple the receptors from their cognate G proteins. Recent studies on the beta2-adrenergic receptor have demonstrated that beta-arrestin also targets the receptors to clathrin-coated pits for subsequent internalization and activation of mitogen-activated protein kinases. We and others have previously shown that muscarinic acetylcholine receptors (mAChRs) of the m1, m3, and m4 subtype require functional dynamin to sequester into HEK-293 tsA201 cells, whereas m2 mAChRs sequester in a dynamin-independent manner. To investigate the role of beta-arrestin in mAChR sequestration, we determined the effect of overexpressing beta-arrestin-1 and the dominant-negative inhibitor of beta-arrestin-mediated receptor sequestration, beta-arrestin-1 V53D, on mAChR sequestration and function. Sequestration of m1, m3, and m4 mAChRs was suppressed by 60-75% in cells overexpressing beta-arrestin-1 V53D, whereas m2 mAChR sequestration was affected by less than 10%. In addition, overexpression of beta-arrestin-1 V53D as well as dynamin K44A significantly suppressed m1 mAChR-mediated activation of mitogen-activated protein kinases. Finally, we investigated whether mAChRs sequester into clathrin-coated vesicles by overexpressing Hub, a dominant-negative clathrin mutant. Although sequestration of m1, m3, and m4 mAChRs was inhibited by 50-70%, m2 mAChR sequestration was suppressed by less than 10%. We conclude that m1, m3, and m4 mAChRs expressed in HEK-293 tsA201 cells sequester into clathrin-coated vesicles in a beta-arrestin- and dynamin-dependent manner, whereas sequestration of m2 mAChRs in these cells is largely independent of these proteins.

Arrestins↗

PubMed1999

Sequence information within proteasomal prosequences mediates efficient integration of beta-subunits into the 20 S proteasome complex.

The maturation of proteases is governed by prosequences. During the biogenesis of the highly oligomeric eukaryotic 20 S proteasome five different prosequence-containing subunits have to be integrated and processed either by autocatalysis or by neighbouring subunits. To analyse the functional impact of proteasomal prosequences during complex formation, the propeptide of the facultative subunit beta1i/LMP2 was truncated to nine amino acid residues or completely deleted. Additionally, the charged residues within the truncated beta1i/LMP2 version were replaced by neutral residues. While deletion did not affect subunit incorporation, the presence of charged residues within the truncated version of the LMP2 propeptide diminished incorporation efficiency, an effect that was restored upon replacement of the charged amino acids against neutral components. During immunoproteasome formation, incorporation and processing of inducible proteasome beta-subunits are cooperative processes. We demonstrate a linear correlation of the levels of beta2i/MECL1 and beta1i/LMP2 within 20 S proteasomes, suggesting a physical interaction to be the molecular basis for the biased incorporation of both subunits. In the absence of beta5i/LMP7, precursor complexes containing unprocessed beta1i/LMP2 accumulated. The contribution of beta5i/LMP7 on the cooperative formation of a homogeneous population of immunoproteasome is therefore most likely based on an acceleration of the beta1i/LMP2 and potentially of beta2i/MECL1 processing kinetics.

Amino Acid Sequence↗

PubMed1999

Tourette syndrome and the norepinephrine transporter gene: results of a systematic mutation screening.

Tourette syndrome (TS) is a complex inherited neuropsychiatric disorder characterized by multiple motor and phonic tics. Involvement of central norepinephrine mechanisms is suggested by central norepinephrinic hyperactivity in patients with TS and by the therapeutic effects of the presynaptic alpha2-adrenergic agonist clonidine. The norepinephrine transporter gene (NET) was systematically screened by single-strand conformation analysis for genetic variants, including the whole coding region and adjacent exon-intron boundaries in 43 patients with TS and 46 healthy controls. We detected 12 DNA sequence variants, among them four missense mutations (Val69Ile, Thr99Ile, Va1245Ile, and Gly478Ser). The observed missense mutations may alter conformational rearrangements during gating of the transporter, assembly of subunits, and norepinephrine-specific uptake affinity. Allele frequency and genotype distribution of the genetic variants showed no differences between TS patients and controls. No mutation of likely functional significance was found that distinguished TS patients from healthy controls, indicating that genetic variants of the NET gene are not causally related to Tourette syndrome.

Adolescent↗

PubMed1999

The ADP-ribosylation factor (ARF)-related GTPase ARF-related protein binds to the ARF-specific guanine nucleotide exchange factor cytohesin and inhibits the ARF-dependent activation of phospholipase D.

ADP-ribosylation factor-related protein (ARP) is a membrane-associated GTPase with remote similarity to the family of ADP-ribosylation factors (ARF). In a yeast two-hybrid screen designed to identify proteins interacting with ARP, we isolated a partial cDNA of the ARF-specific guanine nucleotide exchange factor mSec7-1/cytohesin encoding its N terminus and most of the Sec7 domain (codons 1-200). ARP and ARP-Q79L (GTPase-negative ARP) exhibited a higher affinity to mSec7-1-(1-200) than ARP-T31N (nucleotide exchange-defective ARP) in the two-hybrid assay. Similarly, full-length [35S]mSec7-1/cytohesin was specifically adsorbed to glutathione-Sepharose loaded with glutathione S-transferase (GST)-ARP-Q79L, GST-ARP, or GST-ARP-T31N, the latter exhibiting the lowest binding affinity. Overexpression of ARP-Q79L, but not of ARP-T31N, in COS-7 cells reduced the fluorescence from co-expressed green fluorescent protein fused with mSec7-1/cytohesin or mSec7-2/ARNO in plasma membranes as detected by deconvolution microscopy. Recombinant ARP and ARP-Q79L, but not ARP-T31N, inhibited the phospholipase D (PLD) activity stimulated by mSec7-2/ARNO and ARF in a system of isolated membranes. Furthermore, transfection of HEK-293 cells with ARP or ARP-Q79L, but not ARP-T31N, inhibited the muscarinic acetylcholine receptor-3 induced PLD stimulation and translocation of ARF from cytosol to membranes. These data suggest that the GTP-bound form of ARP specifically binds mSec7-1/cytohesin, and that ARP may be involved in a pathway inhibiting the ARF-controlled activity of PLD.

ADP-Ribosylation Factors↗

PubMed1999

[Bronchial asthma. Symptomless state can be achieved for most patients].

Although we still do not have a cure for bronchial asthma, it has lost much of its terrifying aspect for many sufferers. Thanks to a pathophysiologically rational and individually tailored stepped therapy, 90% of all asthmatics can now be rendered largely symptom-free for most of the time. Such an ambitious goal, however, can be achieved only after first making the greatest diagnostic efforts to identify as many of the triggering agents as possible. To this end, and to enable a rational application of the step-by-step treatment strategy, active cooperation on the part of a patient determined to master his/her problem is mandatory. We can provide him/her with the necessary knowledge and skills by offering appropriate asthma training.

Adrenergic beta-Agonists↗

PubMed1999

Suppression of metastasis formation by a recombinant single chain antibody-toxin targeted to full-length and oncogenic variant EGF receptors.

Cytotoxic strategies which are directed to tumor-associated antigens might be most beneficial for cancer patients with minimal tumor load such as in an adjuvant setting after initial therapy. We have recently described a highly potent single chain antibody-toxin, scFv(14E1)-ETA, which consists of the variable domains of the antibody 14E1 genetically fused to a truncated form of Pseudomonas exotoxin A. ScFv(14E1)-ETA specifically recognizes the human epidermal growth factor receptor (EGFR) and the oncogenically activated receptor variant EGFRvIII, which have been implicated in the development of various human malignancies. Here we have investigated the antimetastatic activity of bacterially expressed scFv(14E1)-ETA and its disulfide-stabilized derivative ds-scFv(14E1)-ETA in a novel model for disseminated disease which is based on murine renal carcinoma cells subsequently transfected with the E. coli beta-galactosidase gene, and human full-length or variant EGFR cDNAs. Intravenous injection of these Renca-lacZ/EGFR and Renca-lacZ/EGFRvIII cells in syngenic Balb/c mice led to the formation of pulmonary metastases which were readily detectable upon excision of the lungs and X-gal staining. Systemic treatment of mice with scFv(14E1)-ETA resulted in the complete suppression of Renca-lacZ/EGFRvIII metastasis formation and drastically reduced the number of pulmonary Renca-lacZ/EGFR tumor nodules. The ds-scFv(14E1)-ETA derivative where the antibody variable regions are connected by an artificial disulfide bond displayed improved thermal stability at physiological temperature but due to reduced cytotoxic activity was less potent than the original scFv(14E1)-ETA in metastasis suppression.

ADP Ribose Transferases↗

PubMed1999

Magnetic resonance imaging of ductus arteriosus Botalli apertus in adulthood.

Ductus arteriosus Botalli apertus is a congenital cardiovascular malformation usually diagnosed in childhood by echocardiography and/or cardiac catheterization. Reports about magnetic resonance imaging of ductus arteriosus Botalli apertus are rare. We report about three adult female patients and one adult male patient in whom magnetic resonance imaging was able to demonstrate the pathology. In all four patients quantitative data about right ventricular function were calculated. Pulmonary hypertension with Eisenmenger syndrome detected by cardiac catheterization had developed in three of the four patients excluding operative closure of the ductus. The patient in whom pulmonary hypertension had not developed underwent successful operative closure of the ductus. Magnetic resonance imaging is a non-invasive tool that can be used for diagnosis of ductus arteriosus Botalli apertus and it allows to quantify right ventricular function. Magnetic resonance imaging can be used repetitively in patients with Eisenmenger syndrome which may be helpful for better timing of combined heart-lung transplantation as ultimate therapeutic strategy because deterioration of right ventricular function can be monitored.

Adult↗

PubMed1999

Temperature-induced production of recombinant human insulin in high-cell density cultures of recombinant Escherichia coli.

The construction of expression vectors encoding either the human insulin A- or B-chains fused to a synthetic peptide and the temperature-induced expression of the recombinant genes in Escherichia coli are reported. Using this two-chain approach we also describe the separate isolation of the insulin A- and B-chains from inclusion bodies and their subsequent assembly into native human insulin. The production of the insulin fusion proteins were carried out in high-cell density fed-batch cultures using a synthetic medium with glucose as sole carbon and energy source. The expression of the recombinant genes by temperature-shift in high-cell density cultures of recombinant E. coli resulted in product yields of grams per litre of culture broth, e.g. 4.5 g of insulin B-chain fusion protein per litre of culture broth. This translates into an expression yield of about 800 mg of the insulin B-chain per litre of culture. Under similar cultivation conditions the expression yield of the insulin A-chain corresponds to approximately 600 mg per litre of culture. The metabolic burden imposed on the recombinant cells during temperature-induced production of insulin fusion proteins in high-cell density cultures is reflected in an increased respiratory activity and a reduction of the biomass yield coefficient with respect to glucose.

Amino Acid Sequence↗

PubMed1999

RecA-dependent viral burst in bacterial colonies during the entry into stationary phase.

We have explored the nature of the sudden viral amplification observed during the ageing of P22-infected lysogenic colonies of Salmonella typhimurium [Ramírez, E, and Villaverde, A. (1997) Gene 202, 147-149]. By a comparative analysis of the wild-type P22 and a P22 integration mutant, it has been shown that the conditions promoting prophage induction occur in only a small portion of the bacterial population and briefly during the transition between the exponential growth and the stationary phase. The viral burst is RecA-dependent and cannot be reproduced in continuous culture by a mere decrease of the growth rate. This suggests that the limited viral propagation in colonies is probably linked to heterogeneous physiological conditions within colonial populations, distinct from those of the homogeneous liquid cultures.

Bacteriophage P22↗

PubMed1999

Allelism of Saccharomyces cerevisiae genes PSO6, involved in survival after 3-CPs+UVA induced damage, and ERG3, encoding the enzyme sterol C-5 desaturase.

Sequencing of the yeast gene that complemented the sensitivity to the photoactivated monofunctional 3-carbethoxypsoralen of the pso6-1 mutant strain revealed that the ERG3 locus, encoding sterol C-5 desaturase involved in biosynthesis of ergosterol, is allelic to PSO6. Disruption of the ERG3 gene yielded an erg3Delta mutant viable in ergosterol-containing YEPD media with the same pleiotropic mutant phenotype known for pso6-1 and erg3 mutants, including sensitivity to hydrogen peroxide and paraquat. Thus, the erg3/pso6 yeast mutant seems to be more sensitive than the WT to 3-CPs+UVA because of the oxidative damage contributed by this treatment and not because of an impaired repair of the furocoumarin-thymine monoadducts formed in the DNA. We found a significant increase of petites amongst erg3Delta and pso6-1 yeast mutant strains grown in conditions where respiration was mandatory. Mutant pso6-1, with its lowered content of ergosterol, exhibited enhanced synthesis of chitin that was maldistributed and not confined to the bud scars. Chitin overproduction in pso6/erg3 mutants resulted in hypersensitivity to Calcofluor White.

Alleles↗

PubMed1999

Ovarian endometrioid-like yolk sac tumor treated by surgery alone, with recurrence at 12 years.

We describe the case of a stage Ia endometrioid-like yolk sac tumor (YST) of the ovary, which was originally misdiagnosed as a malignant struma ovarii and not treated with adjuvant chemotherapy. After 12 years, a contralateral dermoid cyst was excised along with a small omental nodule of partially necrotic and calcified endometrioid-like YST. No tumor was detected in several other biopsy specimens, and a peritoneal lavage was negative for tumor cells. Since there was no evidence of remaining tumor and the serum alpha-fetoprotein (AFP) level was normal after the second operation, the patient was followed. Serial serum AFP levels remained normal for 4 months. At a second-look laparotomy after 4 months, a small tumor nodule was removed from the cul-de-sac. Postoperatively, the patient received three cycles of BEP chemotherapy. The long disease-free interval after the first operation in spite of the presence of occult spread to the omentum and to the pouch of Douglas in this case indicates that some endometrioid-like YSTs may have an indolent course. The present case underscores the importance of careful surgical staging and of long-term follow-up in cases of primitive germ cell tumors of the ovary.

Adult↗

PubMed1999

Activation of a cryptic splice donor in human immunodeficiency virus type-1.

The human immunodeficiency virus type-1 regulatory protein Rev is absolutely required for the production of viral structural proteins. Splice sites have been seen to function as cis-acting repressor sequendes (CRS) and inhibit expression of the Rev-dependent RNAs. In order to analyze the role of a splice donor in Rev dependence, the wild-type 5' splice donor of HIV-1 was mutated in the context of other gag sequences. Following transient transfection, RNA expression by RT-PCR was analyzed. The unspliced RNA produced by the mutant construct still required Rev for the cytoplasmic accumulation of the RNA. Despite deletion of the wild-type 5' splice donor and the tat splice acceptor was used. A cryptic splice donor was identified by PCR and subsequent cloning of the spliced RNA. The cryptic site is 5/9 to the consensus sequence and located immediately downstream of the initiation codon (ATG) for Gag. Analysis of the RNA product containing the cryptic splice donor revealed that the Rev was required for the cytoplasmic accumulation of unspliced RNA, while spliced RNA was Rev independent. Transfection of a wild-type construct also demonstrated usage of the cryptic splice donor. These results indicate that a cryptic splice donor can be activated when the wild-type splice donor is inactivated and that the cryptic splice donor may retain Rev regulation. The findings also suggest the potential for cryptic splice sites to serve as CRS in the determining the Rev dependence of viral RNAs.

Animals↗

PubMed1999

In vitro image characteristics of an abdominal aortic stent graft: CTA versus 3D MRA.

Percutaneous stent-grafting is increasingly employed as a less invasive alternative to surgery for the treatment of infrarenal abdominal aortic aneurysms. It requires long-term imaging follow-up, to document the structural integrity of the device, to exclude perigraft channels and endograft leakages, as well as the shrinkage of the aneurysmal sac. The expectation of severe stent induced artifacts and safety concerns have prevented 3D MRA from being used. The purpose of this in vitro study was to investigate the imaging characteristics of a bifurcated stent graft with 3D MRA (3D Fourier transform fast spoiled GRE) at 1.5 T in comparison to those of CTA. Measurement of the stent wall thickness and luminal diameter were made on a agar gel embedded stent graft at five locations on both CTA and MRA images. The stent graft was depicted as a dark ring on MR images. Wall thickness measurements at the five locations of the stent graft overestimated the true stent thickness, while luminal diameters were slightly underestimated. Measurement differences between MR and CT were not statistically significant (P = 0.67; P = 0.85). Artifacts emanating from the platinum markers were considerably less severe on the MR-images. A wider area of signal loss was seen only at the insertion of the iliac stent leg into the aortic stent portion due to the overlap of two radio-opaque platinum markers. 3D MRA images should permit a comprehensive assessment of the arterial lumen, and of perivascular tissues.

Aortic Aneurysm, Abdominal↗

PubMed1999

Sensitivity and specificity of a screening test to document traumatic experiences and to diagnose post-traumatic stress disorder in ARDS patients after intensive care treatment.

OBJECTIVE: Many survivors of critical illness and intensive care unit (ICU) treatment have traumatic memories such as nightmares, panic or pain which can be associated with the development of posttraumatic stress disorder (PTSD). In order to simplify the rapid and early detection of PTSD in such patients, we modified an existing questionnaire for diagnosis of PTSD and validated the instrument in a cohort of ARDS patients after long-term ICU therapy. DESIGN: Follow-up cohort study. SETTING: The 20-bed ICU of a university teaching hospital. PATIENTS: A cohort of 52 long-term survivors of the acute respiratory distress syndrome (ARDS). INTERVENTIONS AND MEASUREMENTS: The questionnaire was administered to the study cohort at two time points 2 years apart. At the second evaluation, the patients underwent a structured interview with two trained psychiatrists to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The reliability and validity of the questionnaire was then estimated and its specificity, sensitivity and optimal decision threshold determined using receiver operating characteristic (ROC) curve analyses. RESULTS: The questionnaire showed a high internal consistency (Crohnbach's alpha = 0.93) and a high test-retest reliability (intraclass correlation coefficient alpha = 0.89). There was evidence of construct validity by a linear relationship between scores and the number of traumatic memories from the ICU the patients described (Spearman's rho = 0.48, p < 0.01). Criterion validity was demonstrated by ROC curve analyses resulting in a sensitivity of 77.0% and a specificity of 97.5% for the diagnosis of PTSD. CONCLUSIONS: The questionnaire was found to be a responsive, valid and reliable instrument to screen survivors of intensive care for PTSD.

APACHE↗

PubMed1999

Second malignancies after Hodgkin's disease: the Munich experience.

The occurrence of second malignancies (SM) is an important late event following the treatment of Hodgkin's disease (HD). We sought to determine the incidence, the risk factors, and the prognosis of SM in our population of patients with HD. A total of 1120 patients diagnosed with HD were registered at six participating institutions in Munich (calendar period 1974-1994). The mean follow-up for the development of SM was 9.1 years. A cumulative treatment score was calculated for both radio- and chemotherapy. The relative and absolute risks of SM were established. All SM were investigated for response to treatment and outcome. We observed 85 SM [eight leukemias, 22 non-Hodgkin's lymphomas (NHL), two plasma cell neoplasias, and 53 solid tumors]. Five patients developed third malignancies. The relative risk of developing a second neoplasm was compared with that within the normal population and was 3.1-fold. The risk varied according to the category of SM. Higher relative risks (20.5 and 25.9-fold), but lower absolute risks were observed for leukemias and non-Hodgkin's lymphomas. Solid tumors had lower relative risks (1.8-fold). Splenectomy increased the risk of SM (relative risk 4.4-fold versus 2.7-fold). The risk of SM did not correlate with the initial treatment (radio- or chemotherapy) and did not decrease with prolonged follow-up. The cumulative intensity of radiotherapy, chemotherapy, or the two modalities combined correlated with the risk of SM. Since some cases occurred early after diagnosis, not all second neoplasms can be considered treatment-associated. After 15 years, an actuarial risk of 11.7% was calculated for all SM, of 1.0% for leukemias, of 3.0% for NHL, and of 7.7% for solid tumors. The prognosis of SM varied between good (thyroid cancer, melanoma: median survival 5+ years), average (breast cancer, NHL), and poor (acute myeloid leukemias, lung cancers: median survival 9 months). With the exception of NHL, second cancers often occurred in topographic relation to the field of previous radiotherapy. Taken together, in our patient population, we observed all three categories of SM (solid tumors, leukemias, NHL). The risk for second leukemias is lower than in previous studies, whereas the risk of second NHL is somewhat higher. We confirm that splenectomy is a possible risk factor for SM. Even after correction for the age-specific cancer incidence, treatment intensity is associated with the development of second malignant tumors. Continued follow-up is mandatory after treatment for HD. Since the prognosis of most SM is unfavorable, early recognition and prevention are of the utmost importance.

Adolescent↗

PubMed1999

A PC program for estimating organ dose and effective dose values in computed tomography.

Dose values in CT are specified by the manufacturers for all CT systems and operating conditions in phantoms. It is not trivial, however, to derive dose values in patients from this information. Therefore, we have developed a PC-based program which calculates organ dose and effective dose values for arbitrary scan parameters and anatomical ranges. Values for primary radiation are derived from measurements or manufacturer specifications; values for scattered radiation are derived from Monte Carlo calculations tabulated for standard anthropomorphic phantoms. Based on these values, organ doses can be computed by the program for arbitrary scan protocols in conventional and in spiral CT. Effective dose values are also provided, both with ICRP 26 and ICRP 60 tissue-weighting coefficients. Results for several standard CT protocols are presented in tabular form in this paper. In addition, potential for dose reduction is demonstrated, for example, in spiral CT and in quantitative CT. Providing realistic patient dose estimates for arbitrary CT protocols is relevant both for the physician and the patient, and it is particularly useful for educational and training purposes. The program, called WinDose, is now in use at the Erlangen University hospitals (Germany) as an information tool for radiologists and patients. Further extensions are planned.

Dose-Response Relationship, Radiation↗