Biomedical subjects

J Krämer

Publications and source records attributed to J Krämer.

At least 19 recordsLinked to original sources

PubMed2007

Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongly suggest a BCS Class 1 classification. Prednisolone's therapeutic indications and therapeutic index, pharmacokinetics, and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks.

Administration, Oral↗

PubMed2005

Evidence for a neural correlate of a framing effect: bias-specific activity in the ventromedial prefrontal cortex during credibility judgments.

BACKGROUND: Neural processes within the medial prefrontal cortex play a crucial role in assessing and integrating emotional and other implicit information during decision-making. Phylogenetically, it was important for the individual to assess the relevance of all kinds of environmental stimuli in order to adapt behavior in a flexible manner. Consequently, we can in principle not exclude that environmental information covertly influences the evaluation of actually decision relevant facts ("framing effect"). OBJECTIVE: To test the hypothesis that the medial prefrontal cortex is involved into a framing effect we employed functional magnetic resonance imaging (fMRI) during a binary credibility judgment task. METHODS: Twenty-one subjects were asked to judge 30 normalized news magazine headlines by forced answers as "true" or "false". To confound the judgments by formally irrelevant framing information we presented each of the headlines in four different news magazines characterized by varying credibility. For each subject the susceptibility to the judgment confounder (framing information) was assessed by magazine-specific modifications of the answers given. RESULTS: We could show that individual activity changes of the ventromedial prefrontal cortex during the judgments correlate with the degree of an individual's susceptibility to the framing information. CONCLUSION: We found (i) a neural correlate of a framing effect as postulated by behavioral decision theorists that (ii) reflects interindividual differences in the degree of the susceptibility to framing information.

Adult↗

PubMed2005

[Surgical anatomy of the lumbar spine].

The success and risks of spinal surgery depend on a correct diagnosis and detailed knowledge of anatomy. This report provides information on relevant structures of the lumbar spine and possible surgical complications. Anatomical topography and different surgical approaches are described step by step.

Bone Screws↗

PubMed2004

[Osteomyelitis after endoprostheses].

Today over 170,000 total hip arthroplasties and about 70,000 total knee arthroplasties are performed in Germany. An overall infection rate of 0.5-1.4% is reported in the literature. This means that 800-1700 infections after total hip arthroplasty and 300-850 infections after total knee arthroplasty can occur. The surgical treatment of early or late infections after arthroplasty of the hip or knee needs different intervention. Depending on when the infection develops, a simple Débridement, an allinone exchange arthroplasty, or the explantation of the endoprosthesis with implantation of a spacer followed by the reimplantation of a new prosthesis must be performed. The first hint of postoperative infection is the increase of the C-reactive protein. By correct treatment of the postoperative wound the first sign of an infection can be detected early.

Anti-Bacterial Agents↗

PubMed2002

[Low back pain].

Explore the source record for details and available documents.

Diagnosis, Differential↗

PubMed2001

[Intervertebral disk displacement and trauma].

It is difficult to find medical evidence of a correlation between a lumbar disk disease and trauma. One should consider whether the individual degeneration of lumbar disks or the trauma lead to the typical complaints. Disk disease in the population are very common. Therefore the relevance of the individual affection before trauma has to be considered. Spinal trauma with its sudden, incidental onset needs to be differentiated from purposeful and conscious movements. An intervertebral disk disease can be classified as accident related only in cases involving adequate trauma, with no previous complains, and a sudden onset of pain.

Diagnosis, Differential↗

PubMed2001

Lumbar micro disc surgery with and without autologous fat graft. A prospective randomized trial evaluated with reference to clinical and social factors.

Epidural scarring is one of the possible complications after lumbar disc surgery. Perineural scar tissue has been considered responsible for recurrent neurological symptoms in patients operated on for disc herniation and leads to a high rate of unsatisfactory results. In addition, postoperative scars may increase the technical difficulty and risk of subsequent procedures. Various materials have been used in animal studies to try to affect the degree of epidural scar tissue with controversial results. In particular, free fat transplantation has been described to reduce the degree of intraspinal scar tissue. We therefore performed a prospective, double-blind, randomized study comparing clinical and social factors of patients being operated on for the first time for lumbar disc herniation. A total of 92 patients received an implantation of autologous fat graft, 94 did not. After a median of 24.2 months after their surgery, an objective examinator compared various clinical parameters and the social situation of patients in both groups without knowing the operation method used. We found no significant differences between the fat-graft group and the control group regarding either the clinical outcome or the social aspects.

Adipose Tissue↗

PubMed2001

Differentiation of the smooth muscle cell phenotypes during embryonic development of coronary vessels in the rat.

Smooth muscle cell (SMC) maturation during embryonic development of coronary arteries and veins was studied in rats using different markers of the contractile phenotypes. The spatio-temporal pattern of distribution of these markers compared with the developing tunica media was examined. Alpha-smooth muscle actin (alpha-SMA) was the first marker of the SMC in the tunica media of coronary arteries found in ED16 hearts, followed by smooth muscle myosin heavy chain isoform which occurred on ED17. Subsequently 1E12 antigen was expressed in coronary artery wall in ED18 hearts, and finally smoothelin. The markers occur within the proximal part of the coronary arteries and deploy toward the apex. They are also found within the great vessels. None of the markers except for the alpha-SMA were found in coronary veins during embryonic life. We conclude that the SMC population of the developing tunica media of coronary vessels differentiates by the acquisition of particular markers and this process lasts till the end of the prenatal and early postnatal life.

Actins↗

PubMed2001

Determination of renal arterial stenosis severity: comparison of pressure gradient and vessel diameter.

PURPOSE: To determine the hemodynamic significance of arteriographically detected renal arterial stenosis by obtaining pressure gradients with a miniaturized pressure guide wire. MATERIALS AND METHODS: Forty-six renal arterial stenoses in 38 patients were assessed in terms of severity and then subjected to gradient determination before and after angioplasty. The patients (mean age, 63 years) had a mean serum creatinine value of 1.3 mg/dL +/- 0.4 (114.9 micromol/L +/- 35.4 [SD]) and required on average three medications for blood pressure control. The mean degree of stenosis diameter was 51% +/- 17 (range, 12%-85%). RESULTS: The systolic and mean arterial pressure gradients with and those without vasodilatation were highly correlated with stenosis severity, systolic blood pressure, and serum creatinine as a curvilinear fit (r = 0.9, P <.01). At 50% stenosis severity, the mean pressure gradient was 22 mm Hg. CONCLUSION: Patients with a pressure gradient greater than 20 mm Hg should be good candidates for renal arterial dilatation, and use of the pressure guide wire will facilitate interventional decisions.

Adult↗

PubMed2000

[Renovascular illness: prevalence and therapy in patients with coronary heart disease].

To explore the relationship between coronary artery disease and renal vascular disease, we performed renal arterial angiography in 609 patients undergoing coronary angiography for suspected coronary artery disease. We defined renal artery stenosis as nonsignificant (< 40%), borderline (40-60%) and significant (> 60%). One-hundred fifty-two patients had renal artery stenosis, while 457 did not. Two-hundred and ten patients had no coronary disease; of these, only 9 had renal artery stenosis. On the other hand, the 143 patients with renal artery stenosis, when subdivided, had similar degrees of coronary disease; three vessel disease was significantly more common than one or two vessel disease in all groups. Renal artery stenosis of all severity degrees was associated with common atherosclerotic risk factors. However, hypertension was not a clue to the presence of renal artery stenosis. To evaluate the effect of percutaneous revascularization on hypertension and renal function all 51 patients with significant renal artery stenosis were treated by primary stent implantation and were followed up for 6 months. Stent implantation showed a marked decrease in systolic and diastolic blood pressure (163 +/- 30 to 145 +/- 17 and 93 +/- 18 to 83 +/- 10 mmHg; p = 0.008) with a decrease in the amount of antihypertensive medication but without beneficial effect on serum creatinine during follow-up (1.46 +/- 0.70 mg/dl to 1.39 +/- 0.58 mg/dl, p = ns). We conclude that renal artery stenosis of any severity is strongly suggestive of three vessel coronary artery disease. The fact that renal stenting lowers blood pressure decreases antihypertensive drugs and increases medication flexibility in patients with coronary artery disease would support the notion of revascularization in patients with significant stenoses.

Aged↗

PubMed2000

Dissolution testing as a prognostic tool for oral drug absorption: dissolution behavior of glibenclamide.

PURPOSE: The dissolution behavior of two commercially available glibenclamide formulations was tested in various media. The aim of the study was to investigate whether the use of biorelevant dissolution media (BDM) would be advantageous over the use of standard media for predicting the in vivo performance of the two formulations. METHODS: The dissolution tests were performed using USP 23 apparatus 2. Conventional buffers and USP media were compared with two BDM containing different amounts of lecithin and sodium taurocholate. RESULTS: The dissolution of two drug powders was highly dependent on wetting, particle size, pH, and the composition of the medium used. In addition, the dissolution behavior of the two glibenclamide formulations showed differences in all media tested. The dissolution results of the two formulations were compared with those from an in vivo bioequivalence study undertaken by the central quality control laboratory of the German pharmacists (ZL). The bioequivalence criterion set by the ZL requires more than 80% drug release within 10 minutes. Results in FaSSIF, one of the BDMs, met the ZL criterion and this medium was also able to discriminate between the two formulations. This was not the case for the other media tested. CONCLUSIONS: The study indicates that BDM are better able to discriminate between glibenclamide formulations than standard dissolution media.

Administration, Oral↗

PubMed2000

Deoxynivalenol and ochratoxin A in German wheat and changes of level in relation to storage parameters.

The occurrence of the mycotoxins deoxynivalenol (DON) and ochratoxin A (OTA) in the winter wheat of 1997 and 1998 grown under organic farming conditions was investigated using ELISAs (R-Biopharm) for quantification. The influence of delayed drying of the grain after harvest on the development of DON and OTA was determined in storage trials (moisture: 17% and 20%; temperature: 20 degrees C; duration: four and six weeks). The Tox5 PCR assay was used both to detect Fusarium species with the potential to produce trichothecenes and as a measure of their relative DNA content during the storage trials. The intensity of the PCR signals was correlated with the DON concentration. Fusarium species were identified microscopically by standard methods. All the freshly harvested grain samples were contaminated with DON and showed further increases in the DON concentration during storage. OTA contamination was found in 14.3% of the 1997 samples and in 24.1% of the 1998 samples. OTA increased during storage trials of the 1997 samples but not in the 1998 samples.

Enzyme-Linked Immunosorbent Assay↗

PubMed2000

Clinical and angiographic outcome in patients with in-stent restenosis and repeat target lesion revascularisation in small coronary arteries.

OBJECTIVE: To evaluate the clinical and angiographic outcome in patients with in-stent restenosis in small coronary arteries and repeat target lesion revascularisation. DESIGN: Patients with in-stent restenosis in coronary arteries < or = 2.85 mm were eligible for the study and underwent target lesion revascularisation. Clinical and angiographic variables were assessed during a six month follow up period. RESULTS: 73 patients with 79 lesions were treated by percutaneous transluminal coronary angioplasty (47%), excimer laser angioplasty (25%), or restenting (28%). The mean (SD) reference diameter before target lesion revascularisation was 2.12 (0.5) mm. Procedural success was achieved in all cases, but 57% of the patients had restenosis after six months. The rate of further restenosis was higher with laser angioplasty (78%) than with restenting (47%) or balloon angioplasty alone (49%, p < 0.05). CONCLUSIONS: Treatment for in-stent restenosis in small coronary arteries is feasible and safe, with a second restenosis rate comparable to large coronary artery series. The strategy of target lesion revascularisation influences further in-stent restenosis, with an increased rate with laser angioplasty compared with restenting and repeat dilatation alone.

Aged↗

PubMed2000

Synergistic effects of AT(1) and ET(A) receptor blockade in a transgenic, angiotensin II-dependent, rat model.

Angiotensin II and endothelin may participate in increasing blood pressure and inducing end-organ damage, but the evidence is conflicting. We tested the hypothesis that endothelin(A) receptor blockade would ameliorate blood pressure and end-organ damage in a rat model of human renin-dependent hypertension. We studied rats that were transgenic for both the human renin and angiotensinogen genes. Experimental groups (n=12 each) of untreated transgenic rats, transgenic rats receiving subdepressor doses of losartan (10 mg/kg), transgenic rats receiving LU 135252 (30 mg/kg), transgenic rats receiving both drugs, and nontransgenic rats were studied between 6 to 10 weeks of age. Blood pressure was measured with tail-cuff sphygmomanometry. Gene expression for atrial natriuretic peptide, collagen III, and ACE was measured. The mortality rate in untreated transgenic rats was 42%, which is consistent with previous observations in this line. Single losartan or LU 135252 treatment reduced mortality incidence to 1 rat per group (8%), without significantly lowering blood pressure. In the combination group, blood pressure was normalized and all rats survived. The drug combination also decreased elevated water intake in transgenic rats to normal levels and significantly reduced cardiac hypertrophy. Furthermore, the combination of drugs decreased cardiac atrial natriuretic peptide, ACE gene, and renal collagen III gene expression. We suggest that endothelin participates in this model of angiotensin II-induced hypertension and end-organ damage. Our findings may have clinical implications and provide a rationale for combining angiotensin II type 1 receptor and endothelin(A) receptor blockade to obtain a synergistic effect.

Angiotensin II↗

PubMed2000

A novel and robust homogeneous fluorescence-based assay using nanoparticles for pharmaceutical screening and diagnostics.

We have established a new type of homogeneous immunoassay based on nanoparticles (nanoparticle immunoassay, or NPIA) being analyzed using fluorescence intensity distribution analysis (FIDA). This method allows the characterization of single fluorescently labeled molecules or particles with respect to their molecular brightness and concentration. Upon binding of conjugates to molecules coupled to the nanoparticle surface, the brightness of the complex scales with the number of bound conjugates. The complexes can then be distinguished accurately from free conjugate and concentrations of free and bound molecules can be determined reliably. In this study we present various examples of NPIAs where capture antibodies were linked to the nanoparticles, which were either artificial beads or bacteria. Two assay formats have been developed; first, direct labeling of the conjugate was used to quantitate free antigen through competition experiments, and second, an antigen-directed antibody was labeled to establish an assay similar to a sandwich ELISA setup. The major advantages of a NPIA are the robustness and high signal-to-noise ratio at short measurement times, as demonstrated with a miniaturized experiment in a Nanocarriertrade mark holding a volume of 1 microl/well. In addition to the good data quality, NPIAs are straightforward to perform because they require no washing steps. NPIAs open new dimensions for high throughput pharmaceutical screening and diagnostics. Assay development times can be reduced significantly because of a simple toolbox principle that is applicable to most types of assays.

Chorionic Gonadotropin↗

PubMed1999

A novel isoform of the smooth muscle cell differentiation marker smoothelin.

Studies on smooth muscle cell differentiation and those on vascular development in mouse and humans have long been hampered by the lack of suitable markers. Here we describe a novel, large isoform of smoothelin, a structural protein of differentiated, contractile smooth muscle cells. The protein, which is highly conserved in mouse and humans, shows homology with other cytoskeleton-associated smooth muscle cell proteins and contains an actinin-type actin-binding domain. Northern blot analysis from various mouse organs identified short and long smoothelin mRNA forms, which exhibit distinct tissue expression patterns. The short form is highly expressed in visceral muscle tissues such as intestine and stomach and is not detectable in brain, while the long mRNA form is expressed in all vascularized organs. These results may provide new tools and approaches to study both smooth muscle cell differentiation and proliferative vascular disease.

Actinin↗

PubMed1999

[Surgical treatment of lumbar intervertebral disk displacement. Indications and methods].

The decision about operative or non-operative treatment of herniated lumbar discs has to be based on the results of clinical and neurological examination. Results of imaging techniques as CT or MRI are secondary. Various percutaneous endoscopic or open techniques have been described. The most appropriate technique is determined by the anatomical situation of the dislocated lumbar disc tissue. Intradiscal percutaneous therapies such as percutaneous nucleotomy and laser decompression are possible, but they revealed poor results in prospective randomized and controlled studies. Chemonucleolysis remains as an effective intradiscal technique at the time, but is afflicted with side effects and complications. Endoscopic transforaminal or interlaminary techniques are still experimental. Whenever open surgery is necessary, microsurgical techniques are preferred. If a certain technique is to be applied, there has to be the correct indication, technical support for and experience in using the choosen method.

Diskectomy↗

PubMed1999

Malignant hyperthermia causing Gly2435Arg mutation of the ryanodine receptor facilitates ryanodine-induced calcium release in myotubes.

We have investigated if cultivated muscle cells from malignant hyperthermia (MH) patients can be distinguished pharmacologically from controls. Muscle specimens from four individuals carrying the Gly2435Arg mutation of the skeletal muscle ryanodine receptor protein (RYR1) and from four controls were used to culture myotubes. Resting intracellular calcium concentration ([Ca2+]i) of MH myotubes was similar to controls. However, when ryanodine 0.5 mumol litre-1 was added, the kinetics of the increase in the calcium signals in MH and control cells were significantly different; the time for half maximum increase was mean 197 (SD 131) s for MH cells and 474 (61) s for controls (n = 80 cells each). On average, the area under the MH response curves was twice the control value. These results give rise to hopes that the phenotype of MH can be characterized using cultured human muscle and that a culture-based test for MH susceptibility may eventually be developed.

Adolescent↗