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P Koenig

Publications and source records attributed to P Koenig.

At least 19 recordsLinked to original sources
PubMed2005

Development of a fluorescence-based assay for screening of modulators of human organic anion transporter 1B3 (OATP1B3).

The organic anion transporting protein 1B3 (OATP1B3), formerly termed OATP8, is responsible for uptake and subsequent elimination of multiple amphipathic drugs by the liver. In silico methods for the prediction of transport rates for drugs and drug-like molecules might provide an important tool in drug development. Most prediction methods however require a large training set of in vitro experimental data in order to yield reliable results. To obtain these data, we have developed a fluorescence-based assay that allows screening a relatively high number of substances for their transporter affinity. HEK293 cells overexpressing OATP1B3 (HEK-OATP8) [Y. Cui, J. Konig, D. Keppler, Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2, Mol. Pharmacol. 60 (2001) 934-943.] were tested for transport of Fluo-3. Fluo-3 uptake could be seen in a concentration-dependent manner. Uptake can be inhibited completely by the addition of the known OATP1B3-inhibitor rifampicin proving that Fluo-3 is transported by OATP1B3. To verify the suitability of the system to identify modulators of OATP1B3, we tested known substrates for competitively inhibiting the Fluo-3 transport by giving them simultaneously with a 2muM Fluo-3-solution to the cells. The transport of Fluo-3 was decreased by all test substrates in a concentration dependent manner.

Aniline Compounds↗
PubMed2001

Immediate and six-month results of the profile of the Amplatzer septal occluder as assessed by transesophageal echocardiography.

Catheter closure of secundum atrial septal defect (ASD) using the Amplatzer septal occluder (ASO) is a potential alternative for open surgical repair. However, the large profile of the device obtained immediately after closure continues to raise some concerns regarding its long-term safety. To evaluate the changes in the profile of the device after being deployed, transesophageal echocardiography was performed in 70 patients (17 men and 53 women) who underwent catheter closure of ASDs immediately after and at 6-month follow-up. The median age at closure was 16 years (range 1.9 to 75) and the median size of the ASD as assessed by transesophageal echocardiography was 14 mm (range 3 to 25). The thickness (profile) of the device was assessed in the 4-chamber, short- and long-axis views of the interatrial septum, and measured at its middle and at the junction of the waist with the disc at its 2 ends. Seventy-three devices were deployed in the 70 patients. The median size of the device was 19 mm (range 8 to 34). Complete closure was achieved in 81.4% and 91.4% immediately after and at 6-months follow-up, respectively. The thickness of the device at its middle decreased from 12.2 +/- 4.3, 12.2 +/- 3.7, and 12.5 +/- 4.3 mm in the 4-chamber, short- and long-axis views to 6.5 +/- 2.0, 6.3 +/- 1.9, and 6.5 +/- 2.2 mm, respectively. The thickness of the device at its superior, inferior, anterior, and posterior edges also decreased by 41.8% +/- 14.0% to 43.7% +/- 9.8%. The changes in the thickness were related to device size. Larger devices were thicker after being deployed. We conclude that the thickness of the ASO decreases by 42% to 48% within 6 months after deployment, resulting in a lower profile.

Adolescent↗
PubMed2001

Transcatheter closure of atrial septal defects and patent foramen ovale under intracardiac echocardiographic guidance: feasibility and comparison with transesophageal echocardiography.

Transesophageal echocardiography (TEE) has been employed successfully for guiding transcatheter device closure of secundum atrial septal defect (ASD) and patent foramen ovale (PFO). However, the use of TEE for device closure requires general anesthesia. Intracardiac echocardiography (ICE) can provide similar anatomical views that might replace the use of TEE for device closure. Eleven patients (eight female/three male) with secundum ASD and PFO associated with strokes underwent attempts at transcatheter closure of their defects under sequential TEE and ICE guidance (six patients) and under ICE alone (five patients). The ages of the patients ranged from 6.6 to 74.7 yr, and their weights ranged from 23 to 124.5 kg. The sizes of the defects, as measured by TEE (six patients), ranged from 3 to 27 mm and, as measured by ICE (11 patients), from 3 to 27 mm. The balloon-stretched diameter of the ASD, as measured by TEE (six patients), ranged from 16 to 38 mm and, as measured by ICE (11 patients), from 16 to 35 mm. Both techniques correlated well for the measured two-dimensional diameter and for the balloon-stretched diameter (r = 0.97 and 0.98, respectively). Both TEE and ICE provided similar views of the defects and the various stages of device deployment. Owing to the proximity of the left atrium to the esophagus, however, the images obtained by ICE were more helpful and informative than those obtained by TEE. All patients experienced successful device placement (six patients under both TEE and ICE; five patients under ICE guidance alone); complete closure of the defects was effected in nine patients, whereas two patients had small residual shunts. There were no complications. We conclude that ICE provides unique images of the atrial communications and measurements similar to those obtained by TEE. ICE potentially could replace TEE as a guiding imaging tool for ASD and PFO device closure, thus eliminating the need for general anesthesia.

Adolescent↗
PubMed2001

A rule-based categorization deficit in Alzheimer's disease?

This study examined the categorization processes that Alzheimer's disease (AD) patients use during assessments of semantic memory. Rule-based categorization involves the careful, analytic processing of strict criteria to determine category membership, particularly for items from graded categories with ambiguous category membership; similarity-based categorization requires an overall comparison of a test stimulus with a prototype or remembered exemplar of the category and is relatively effective for the rapid categorization of items with unambiguous category membership. To assess these processes in AD, patients were asked to decide the category membership of test stimuli for categories with poorly defined or fuzzy boundaries (e.g., VEGETABLE) and for categories with well-defined boundaries (e.g., FEMALE) and then to judge the representativeness of the test stimulus for its chosen category. A subgroup of AD patients demonstrated a typical pattern of impaired semantic memory compared to healthy control subjects; that is, difficulty deciding the category membership of test items from fuzzy categories. Among these patients, we found no deficit in category membership decisions about items taken from well-defined categories. We also found that AD patients and healthy controls do not differ in their representativeness judgments of items within a correctly judged category. These findings are most consistent with the hypothesis that rule-based categorization difficulty limits semantic memory in AD.

Aged↗
PubMed1998

About 8-hour variation of circulating human endothelin-1.

Plasma endothelin-1 (ET-1) and cortisol were measured around the clock at hourly intervals on 7 clinically healthy, diurnally active, nocturnally resting subjects 22-27 years of age. The circadian rhythm in cortisol is demonstrated for each subject (p < or = 0.020) as well as on a group basis (p = 0.002), peaking in the morning. By contrast, the circadian variation of ET-1 is statistically significant in only one of the subjects, and it is not detected for the group as a whole (p > 0.20). Instead, ET-1 is characterized by an about 8-h component (p < 0.001) that is not found for cortisol.

Adult↗
PubMed1997

Magnetic resonance imaging compared with echocardiography in the evaluation of pulmonary artery abnormalities in children with tetralogy of Fallot following palliative and corrective surgery.

BACKGROUND: Abnormalities of the pulmonary arteries following palliative or corrective surgery for tetralogy of Fallot (TOF) are common. Our purpose was to compare the usefulness of magnetic resonance imaging (MRI) and echocardiography in the post- operative evaluation of the pulmonary arteries in children with TOF. OBJECTIVE: Our hypothesis was that MRI is more sensitive than echocardiography in the detection of branch pulmonary artery abnormalities in children with TOF. MATERIALS AND METHODS: Pulmonary artery MRI and echocardiography were performed in 20 children following palliative and/or corrective surgery for TOF. MRI and echocardiography were compared in their ability to detect abnormalities of the pulmonary arteries. Angiographic or surgical correlation was available in 15 children. A perfusion scan for confirmation of pulmonary artery patency was available in one additional child. RESULTS: Abnormalities of the branch pulmonary arteries identified by MRI included: absence or occlusion (2), focal stenosis (15), hypoplasia (2), aneurysm (1), and non-confluence (1). Echocardiography could not adequately visualize the right and left branch pulmonary arteries in eight and ten children, respectively. Echocardiography missed stenosis in 13 branch pulmonary arteries, patency of hypoplastic pulmonary arteries in two children, non-confluence of the pulmonary arteries in one child, and a left pulmonary artery aneurysm in one child. Abnormalities identified by MRI were confirmed in 16 children by angiography, surgery or perfusion scan. CONCLUSION: MRI is more sensitive than echocardiography for the evaluation of branch pulmonary artery abnormalities in children following surgery for TOF.

Adolescent↗
PubMed1997

Patterns of hepatitis C viremia in patients receiving hemodialysis.

OBJECTIVES: Chronic hepatitis C virus (HCV) infection is common in patients who receive hemodialysis (HD). The aim of this study was to determine the natural history of hepatitis C viremia and the clinical utility of quantitation and genotyping of HCV in this population of patients. METHODS: Consecutive sera from two groups of HD patients who were HCV RNA positive, a group of 33 patients treated with interferon alfa (5 MU, three times a week for 4 months) and a group of 31 untreated patients, were analyzed by qualitative polymerase chain reaction, quantitative polymerase chain reaction, and a line probe assay for genotyping. RESULTS: Serum HCV RNA was detected continuously in 20 of 31 untreated patients (65%), and 11 patients (35%) showed a fluctuating pattern of viremia with virus-free intervals of up to 4 wk. Twenty-five of 33 patients (76%) treated with interferon alfa became HCV RNA negative during therapy; eight of these 25 patients had a breakthrough, which was transient in seven patients and persistent in one. Of the remaining 24 end-of-treatment responders, 17 relapsed after completion of therapy, and seven (21%) had a sustained response with undetectable serum HCV RNA for 1 yr of follow-up. Initial serum HCV RNA levels in HD patients were generally low (median, 1 x 10(5) genome eq/ml). Sustained responders had significantly lower median levels of viremia (4 x 10(4) eq/ml) than relapsers and nonresponders (9 x 10(4) and 1.8 x 10(5) eq/ml, respectively). Genotyping revealed a predominance of genotype 1a (33%) and 1b (48%). CONCLUSIONS: This study documents that fluctuating hepatitis C viremia with periods of undetectable HCV RNA is common and that low viral load predicts a sustained response to interferon therapy in HD patients. Diagnosis of chronic hepatitis C and monitoring of interferon therapy in HD patients should include initial HCV RNA quantitation and repeated qualitative measurements of HCV RNA.

Adult↗
PubMed1990

[Double photon absorptiometry in renal osteodystrophy].

Bone mineral content (BMC) of the lumbar spine (L2-L4), femoral neck, Ward's triangle and the trochanteric region was measured in 52 consecutive patients on maintenance haemodialysis. In the whole group the median BMC value as percentage of sex- and age-matched normal means was significantly decreased only in Ward's triangle (91.7%; p less than 0.02). In patients with chronic interstitial nephritis there was a significant decrease in bone density in Ward's triangle and the trochanteric region (p less than 0.02). There was no correlation between BMC and time on dialysis or intact parathormone. BMC value did not predict the type of renal osteodystrophy, according to Delling. 17 patients underwent a second investigation after one year. There was a slight fall in mean BMC of the lumbar spine (-0.9%) and Ward's triangle (-1.1%). The fall in mean BMC of the trochanteric region was pronounced (-3.2%). We believe that the observed low demineralisation, which was more pronounced in patients with interstitial nephritis, may be attributable to early and carefully monitored therapy with vitamin D metabolites.

Absorptiometry, Photon↗
PubMed1986

Status of stroke patients: a community assessment.

The identification of norms relating to the status of stroke patients is significant to community plans to provide contemporary health services for stroke patients. This two-phase research study assessed the status of stroke patients for a large metropolitan area. The first phase of research was a retrospective hospital record review conducted on 1,665 subjects admitted to 13 Cincinnati hospitals with the primary diagnosis of stroke. This study showed that the Cincinnati outcomes were consistent with the outcomes demonstrated in the literature. The most typical stroke patient was a 71-year-old woman with right hemiplegia, who was living at home with another adult after spending 17.5 days in the acute care hospital. The behavioral functional levels of 105 disabled stroke patients were assessed in the second phase, using the Level of Rehabilitation Scale. Subjects were analyzed in five functional areas to determine their level of independent living. Demographic data were used to analyze the findings in comparisons. In general, stroke patients function higher in activities of daily living than they do in social interactions. Stroke patients living with another adult demonstrated a lower degree of functioning in activities of daily living than those who lived alone, but scored higher in social interactions.

Activities of Daily Living↗