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Biomedical subjects

M Kroll

Publications and source records attributed to M Kroll.

At least 19 recordsLinked to original sources

Prevalence of two tumor necrosis factor gene polymorphisms in premature infants with early onset sepsis.

BACKGROUND: Tumor necrosis factor (TNF) is a central mediator of sepsis. The NcoI polymorphism within the TNF locus has been described as a prognostic marker for mortality in adult patients with sepsis. OBJECTIVES: The aim of our study was to investigate the genotype and allele distribution of 2 TNF gene polymorphisms in preterm infants <32 weeks of gestational age, who developed early-onset sepsis. METHODS: A double-blinded retrospective cohort study was carried out on stored Guthrie blood spot cards with group A including 67 premature infants <32 weeks of gestational age with proven early-onset sepsis and group B including 102 healthy newborn infants (>32 + 0 weeks of gestation). The genotype andallele distribution of the study population were also compared to reference groups of healthy adult volunteers (n = 252 for TNF-beta NcoI and n = 233 for -308 TNF-alpha promoter). Polymorphisms of the TNF-alpha promoter -308 region and the NcoI site of the TNF-beta gene were assessed using PCR followed by melting curve analysis or NcoI digestion. The groups were compared by estimation of Hardy-Weinberg equilibrium. RESULTS: The overall allele frequency and genotype distribution of the -308 TNF-alpha and NcoI polymorphism of the TNF-beta gene were comparable to the values found in the controls. CONCLUSION: The study results suggest that none of the analyzed TNF gene polymorphisms may serve as a prognostic marker for preterm infants at high risk of sepsis.

Adult↗

A randomized trial of Korodin Herz-Kreislauf-Tropfen as add-on treatment in older patients with orthostatic hypotension.

In a randomized, double-blind, placebo-controlled, parallel group, phase III clinical trial efficacy and safety of Korodin, a combination of natural D-camphor and an extract from fresh crataegus berries, was investigated in patients 50 years and older with orthostatic hypotension. At visit 1 eligibility of patients was checked and a placebo medication was given to all patients. At visit 2 orthostatic hypotension had to be reconfirmed, then the patient was randomized either to Korodin or placebo, study medication (25 drops) was applied once and then outcome was measured. After 7 days of home treatment with daily 3 x 25 drops outcome was measured at visit 3. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were documented 10, 5, 2 and 0 min before as well as 1, 3, 5, 8, and 10 min after getting in the upright position at visit 1, at visit 2 before and after application of study medication and at visit 3. Primary outcome was the change of mean arterial blood pressure (MAP) from just before standing up to the nadir within the first 3 min after standing up. Secondary outcome variables were SBP, DBP, HR, quality of life (SF-12) and seven typical signs and symptoms of orthostatic hypotension. The study was performed in a rehabilitation clinic and in two doctor's practices in Germany from November 2002 to May 2003. During this time, 57 patients were admitted to the study, 39 patients were eligible and randomized, 38 patients were treated according to protocol and evaluated, 21 patients with Korodin and 17 patients with placebo. After a single application the median decrease of MAP was 11.4 mmHg for Korodin and 14.0 mmHg for placebo. Compared to baseline, the median MAP improved 4.3 mmHg for Korodin and 0.3 mmHg for placebo. After 1 week of treatment the decrease of median MAP after standing up was 9.3 mmHg for Korodin and 13.3 mmHg for placebo. Compared to baseline, the improvement was 5.9 mmHg for Korodin and 1.6 mmHg for placebo. Efficacy of 1 week treatment was significant. For the single application a superiority of Korodin over placebo was seen; however, it was not significant. All secondary outcome variables confirmed these findings, except for the physical summary score in the quality of life evaluation (SF-12 questionnaire). Only one adverse event occurred, but this was not serious and without relationship to the study medication. The other safety variables (SBP, DBP, HR, ECG, physical examination) did not show any problems. This study demonstrates that Korodin is efficacious for orthostatic hypotension in patients over 50 years.

Aged↗

[A solution to add digital signatures to medical images according to the DICOM standard: embedded systems].

Radiology departments often underestimate the importance of protecting medical data during transmission, including the precautions taken to ensure data protection. In teleradiology, transmitted as well as stored patient data have to be signed digitally according to the currently valid regulation (Rontgenverordnung, RoV). The DICOM standard facilitates a digital signature. So far, medical image manufacturers only announced to support this security feature. We introduce a solution that extends the feature of digital signing to older modalities.

Computer Communication Networks↗

Automated mass detection in contrast-enhanced CT colonography: an approach based on contrast and volume.

The purpose of this feasibility study was to design and test an algorithm for automating mass detection in contrast-enhanced CT colonography (CTC). Five patients with known colorectal masses underwent a pre-surgical contrast-enhanced (120 ml volume 1.6 g iodine/s injection rate, 60 s scan delay) CTC in high spatial resolution (16-slice CT: collimation: 16x0.75 mm, tablefeed: 24 mm/0.5 s, reconstruction increment: 0.5 mm). A CT-density- and volume-based algorithm searched for masses in the colonic wall, which was extracted before by segmenting and dilating the colonic air lumen and subtracting the inner air. A radiologist analyzed the detections and causes of false positives. All masses were detected, and false positives were easy to identify. Combining CT density with volume as a cut-off is a promising approach for automating mass detection that should be further refined and also tested in contrast-enhanced MR colonography. More information under http://www.screening.info.

Aged↗

Phase- and size-adjusted CT cut-off for differentiating neoplastic lesions from normal colon in contrast-enhanced CT colonography.

A computed tomography (CT) cut-off for differentiating neoplastic lesions (polyps/carcinoma) from normal colon in contrast-enhanced CT colonography (CTC) relating to the contrast phase and lesion size is determined. CT values of 64 colonic lesions (27 polyps <10 mm, 13 polyps > or =10 mm, 24 carcinomas) were determined by region-of-interest (ROI) measurements in 38 patients who underwent contrast-enhanced CTC. In addition, the height (H) of the colonic lesions was measured in CT. CT values were also measured in the aorta (A), superior mesenteric vein (V) and colonic wall. The contrast phase was defined by xA + (1-x)V using x as a weighting factor for describing the different contrast phases ranging from the pure arterial phase (x=1) over the intermediate phases (x=0.9-0.1) to the pure venous phase (x=0). The CT values of the lesions were correlated with their height (H), the different phases (xA+(1-x)V) and the ratio [xA+(I-x)V]/H. The CT cut-off was linearly adjusted to the imaged contrast phase and height of the lesion by the line y=m[xA+(1-x)V]H+y(0). The slope m was determined by linear regression in the correlation (lesion approximately [xA+(i-x)V]/H) and the Y-intercept y(0) by the minimal shift of the line needed to maximize the accuracy of separating the colonic wall from the lesions. The CT value of the lesions correlated best with the intermediate phase: 0.4A + 0.6V (r=0.8 for polyps > or =10 mm, r=0.6 for carcinomas, r=0.4 for polyps <10 mm). The accuracy in the differentiation between lesions and normal colonic wall increased with the height implemented as divisor, reached 91% and was obtained by the dynamic cut-off described by the formula: cut-off (A,V,H)=1.1 [0.4A+0.6V]/H+69.8. The CT value of colonic polyps or carcinomas can be increased extrinsically by scanning in the phase in which 0.4A + 0.6V reaches its maximum. Differentiating lesions from normal colon based on CT values is possible in contrast-enhanced CTC and improves when the cut-off is adjusted (normalized) to the contrast phase and lesion size.

Adult↗

Patient data security in the DICOM standard.

The DICOM committee added the section "Security Profiles" to the DICOM standard, in order to provide the opportunity of safe communication between health care system partners. Data complying with the DICOM standard--e.g. pictures, signals or reports of examinations can be provided with one or more digital signatures. Attention should be paid to the fact that these possibilities of the DICOM standard are available or can be supplied subsequently by new acquisitions of radiological modalities. The required information to check these prerequisites are given.

Algorithms↗

[Does the digital signature of the DICOM standard meet the requirements of German law?].

The DICOM standard offers the possibilities to generate electronic signatures, valid according to German laws. This enhances the reliability of the correlation between image and patient data. However, only so called qualified electronic signatures--conveniently issued by an accredited supplier--are permissible and not rejectable as evidence in German jurisdiction and are completely equivalent to the handwritten signatures. These qualified electronic signatures can be executed only by individuals, whereas the former are not applicable to technical apparatus like image generating modalities. In consequence, a modality is able to provide its pictures with a "common or advanced signature" solely. This limits the use of the digital signature of the DICOM standard for further applications, e.g. the verifiability within the teleradiology.

Algorithms↗

Thyroid function in healthy and sick very-low-birth-weight infants--thyrotropin and free thyroxine levels until the sixth week of age.

Hypothyroxinemia in preterm infants without congenital hypothyroidism is associated with developmental delay. Longitudinal information on thyroid function in very-low-birth-weight (VLBW, <1,500 g birth weight) infants is limited: we present data on thyroid function in sick and healthy VLBW infants until 6 weeks of age. Free T(4) and TSH levels routinely obtained on days 14-21 and days 35-49 in 92 consecutive VLBW infants were correlated retrospectively with neonatal morbidity. Free T(4) levels were positively correlated with gestational age; an independent effect of neonatal disease on thyroid function was not detectable.

Aging↗

Inducible NF-kappaB activation is permitted by simultaneous degradation of nuclear IkappaBalpha.

Signal-induced phosphorylation and ubiquitination of IkappaBalpha targets this inhibitor of NF-kappaB for proteasome-mediated degradation, thus permitting the release of active NF-kappaB. Upon cell stimulation, NF-kappaB activation results in neotranscription and neosynthesis of its own inhibitor, IkappaBalpha. As reported earlier, the neosynthesized inhibitor is then accumulated in the nucleus, where it rapidly binds to and terminates the function of nuclear NF-kappaB upon withdrawal of the stimulus. The present work was aimed at understanding how NF-kappaB activity is preserved while stimuli persist, despite intense, simultaneous IkappaBalpha neosynthesis, which would be expected to end NF-kappaB activity. We here show that incoming IkappaBalpha in the nucleus represents a target for resident nuclear proteasome complexes. Signal-induced, proteasome-dependent degradation of phosphorylated and ubiquitinated IkappaBalpha occurs in the nucleus, thus permitting the onset and persistence of NF-kappaB activity as long as stimulation is maintained. Our results suggest that intranuclear proteolysis of IkappaBalpha is necessarily required to avoid self-termination of NF-kappaB activity during cell activation.

Cell Nucleus↗

ICD waveform optimization: a randomized, prospective, pair-sampled multicenter study.

The theoretical tissue model-based estimates of phase 1 and phase 2 duration of biphasic waveforms are considerably shorter than the pulse widths currently used in ICDs with standard tilt. This study used a tissue resistance/capacitance (RC) model to identify optimal biphasic pulse widths. By paired step-down defibrillation threshold (DFT) testing, the efficacy of standard versus "tuned" biphasic waveforms was evaluated in 91 patients. Standard waveforms consisted of a phase 1 set to 65% tilt and phase 2 = phase 1. The tuned waveform was based on an RC model of membrane characteristics with a time constant of 3.5 ms. The optimal phase 1 truncation point is at the peak of membrane response. The optimal phase 2 duration ends with a membrane response near or just below 0. In paired analysis, no significant differences were found in DFT or impedance between standard and tuned waveforms. In patients with DFTs > 400 V, the tuned waveform lowered the DFT by an average of 38 V (P < 0.05). Multivariate analyses showed a significant inverse relationship between DFT and impedance (P < 0.001). As impedance increased, the tuned waveform was associated with DFTs comparable to the standard waveform with shorter pulse duration and lower delivered energy. No single tilt value allowing an easy calculation of delivered energy was related to ICD waveform efficacy. The use of ICDs with tuned optimal pulse durations offer a greater flexibility of choice for patients with high DFTs.

Aged↗

Thyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide.

BACKGROUND: Thyroid function disorders have often been observed in preterm infants after intravenous administration of iodinated contrast medium. The effect on thyroid function depends on the dosage, but the choice of the contrast medium may be equally important, as there are appreciable pharmacological differences between them. METHOD: Thyroid function was analysed in 20 very low birthweight infants of gestational age less than 30 weeks after injection of iopromide, a monomeric non-ionic iodinated contrast medium. Levels of free thyroxine and thyroid stimulating hormone were compared with those in 26 control infants. RESULTS: Free thyroxine levels in all study infants ranged from 9.0 to 25.7 pmol/l (days 14-21) and 9.0 to 23.2 pmol/l (days 35-49), and thyroid stimulating hormone levels ranged from 0.13 to 0.26 mU/l (days 14-21) and 0.26 to 11.11 mU/l (days 35-49). These levels were not altered after injection of iopromide. CONCLUSION: The risk of transient hypothyroidism or hyperthyrotropinaemia may be reduced with the use of iopromide compared with other contrast media.

Case-Control Studies↗

Missouri practitioners show notable improvement in diabetic kidney disease screenings.

Missouri practitioners participating in a cooperative Diabetic Kidney Disease Project, organized by the Missouri PRO, showed significant improvement in screening for nephropathy among diabetic patients following a quality improvement intervention. This project provides a solid basis for the National Diabetes Project initiated by HCFA as part of the PRO's Sixth Statement of Work.

Diabetic Nephropathies↗

Prescription attitudes among gynecologists towards two particular risk factors of osteoporosis: the patient's age and her bone mineral density.

OBJECTIVE: The present report assesses, among Belgian gynecologists, the effect of age and bone mineral density on osteoporosis prescription strategy in postmenopausal women. METHODS: Charts of postmenopausal women were summarized. We constructed cases by modifying some parameters. Ten years of age were added or subtracted to the real age of the patient. The bone mineral density (BMD) result was also modified (three levels: normal BMD, osteopenia, osteoporosis). A total of 612 cases were constructed. Twelve cases were sent out of these 612 files to every Belgian gynecologist (n = 1010). For each chart the gynecologists were asked whether they would treat the patient with HRT. They were also asked whether they would prescribe other therapies than HRT and if so, which ones. RESULTS: The chance to have an osteoporosis prevention or treatment prescribed increased when BMD decreased (respectively 57.4% for normal BMD, 73.1% for osteopenia cases and 89.4% for osteoporosis cases; P < 0.001). HRT was the most frequently prescribed medication (67% of the cases), but its prescription rate does not reflect only osteoporosis prevention. Nevertheless, for similar cases with osteopenia, the HRT prescription rate increased by a factor 1.25 and for similar cases with osteoporosis, HRT prescription rate increased by a factor 1.39. Calcium was the 2nd most frequent prescribed regimen. It was prescribed in 17% of the cases. A 3.4-fold increase for osteopenia cases and 7.6-fold increase for osteoporosis cases was observed, compared to women with normal BMD. When calcium was prescribed, it was in association with HRT in 64% of the osteopenia cases and in 76% of osteoporosis cases. Other drugs were less often prescribed. For the "younger age group", that is, with a mean age of 55 years, a prescription rate of 82.9% for any osteoporosis regimen was reached, whereas in the age group that was 10 years older a 20% lower prescription rate was reached (62.6%, P < 0.001). This was mostly due to a decrease in HRT prescription. CONCLUSIONS: Prescription of medication known to reduce osteoporosis occurred more often in cases with low BMD. In the older patients with osteoporosis, gynecologists prescribed HRT less frequently. This was not compensated by a higher prescription rate of other medication.

Adult↗

Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP.

Activation of NF-kappaB transcription factors requires phosphorylation and ubiquitin-proteasome-dependent degradation of IkappaB proteins. We provide evidence that a human F-box protein, h-betaTrCP, a component of Skp1-Cullin-F-box protein (SCF) complexes, a new class of E3 ubiquitin ligases, is essential for inducible degradation of IkappaBalpha. betaTrCP associates with Ser32-Ser36 phosphorylated, but not with unmodified IkappaBalpha or Ser32-Ser36 phosphorylation-deficient mutants. Expression of a F-box-deleted betaTrCP inhibits IkappaBalpha degradation, promotes accumulation of phosphorylated Ser32-Ser36 IkappaBalpha, and prevents NF-kappaB-dependent transcription. Our findings indicate that betaTrCP is the adaptor protein required for IkappaBalpha recognition by the SCFbetaTrCP E3 complex that ubiquitinates IkappaBalpha and makes it a substrate for the proteasome.

Cell Cycle Proteins↗

The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasome.

BACKGROUND: The fungal epipolythiodioxopiperazine metabolite gliotoxin has a variety of toxic effects such as suppression of antigen processing, induction of macrophagocytic apoptosis and inhibition of transcription factor NF-kappaB activation. How gliotoxin acts remains poorly understood except that the molecule's characteristic disulfide bridge is important for immunomodulation. As this fungal metabolite stabilizes the NF-kappaB inhibitor IkappaBalpha in the cytoplasm, we decided to investigate its molecular mechanism of action. RESULTS: We show that gliotoxin is an efficient, noncompetitive inhibitor of the chymotrypsin-like activity of the 20S proteasome in vitro. Proteasome inhibition can be reversed by dithiothreitol, which reduces gliotoxin to the dithiol compound. In intact cells, gliotoxin inhibits NF-kappaB induction through inhibition of proteasome-mediated degradation of IkappaBalpha. CONCLUSIONS: Gliotoxin targets catalytic activities of the proteasome efficiently. Inhibition by gliotoxin may be countered by reducing agents, which are able to inactivate the disulfide bridge responsible for the inhibitory capacity of gliotoxin.

Cells, Cultured↗